Emerging role of tumor-associated macrophages as therapeutic targets in patients with metastatic renal cell carcinoma

Tumor-associated macrophages (TAMs) derived from peripheral blood monocytes recruited into the renal cell carcinoma (RCC) microenvironment. In response to inflammatory stimuli, macrophages undergo M1 (classical) or M2 (alternative) activation. M1 cells produce high levels of inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-12, IL-23 and IL-6, while M2 cells produce anti-inflammatory cytokines, such as IL-10, thus contributing to RCC-related immune dysfunction. The presence of extensive TAM infiltration in RCC microenvironment contributes to cancer progression and metastasis by stimulating angiogenesis, tumor growth, and cellular migration and invasion. Moreover, TAMs are involved in epithelial–mesenchymal transition of RCC cancer cells and in the development of tumor resistance to targeted agents. Interestingly, macrophage autophagy seems to play an important role in RCC. Based on this scenario, TAMs represent a promising and effective target for cancer therapy in RCC. Several strategies have been proposed to suppress TAM recruitment, to deplete their number, to switch M2 TAMs into antitumor M1 phenotype and to inhibit TAM-associated molecules. In this review, we summarize current data on the essential role of TAMs in RCC angiogenesis, invasion, impaired anti-tumor immune response and development of drug resistance, thus describing the emerging TAM-centered therapies for RCC patients.     

Uniparental Genetic Heritage of Belarusians: Encounter of Rare Middle Eastern Matrilineages with a Central European Mitochondrial DNA Pool

Ethnic Belarusians make up more than 80% of the nine and half million people inhabiting the Republic of Belarus. Belarusians together with Ukrainians and Russians represent the East Slavic linguistic group, largest both in numbers and territory, inhabiting East Europe alongside Baltic-, Finno-Permic- and Turkic-speaking people. Till date, only a limited number of low resolution genetic studies have been performed on this population. Therefore, with the phylogeographic analysis of 565 Y-chromosomes and 267 mitochondrial DNAs from six well covered geographic sub-regions of Belarus we strove to complement the existing genetic profile of eastern Europeans. Our results reveal that around 80% of the paternal Belarusian gene pool is composed of R1a, I2a and N1c Y-chromosome haplogroups – a profile which is very similar to the two other eastern European populations – Ukrainians and Russians. The maternal Belarusian gene pool encompasses a full range of West Eurasian haplogroups and agrees well with the genetic structure of central-east European populations. Our data attest that latitudinal gradients characterize the variation of the uniparentally transmitted gene pools of modern Belarusians. In particular, the Y-chromosome reflects movements of people in central-east Europe, starting probably as early as the beginning of the Holocene. Furthermore, the matrilineal legacy of Belarusians retains two rare mitochondrial DNA haplogroups, N1a3 and N3, whose phylogeographies were explored in detail after de novo sequencing of 20 and 13 complete mitogenomes, respectively, from all over Eurasia. Our phylogeographic analyses reveal that two mitochondrial DNA lineages, N3 and N1a3, both of Middle Eastern origin, might mark distinct events of matrilineal gene flow to Europe: during the mid-Holocene period and around the Pleistocene-Holocene transition, respectively.     

Mouthpart morphology and feeding behavior of the invasive kudzu bug,Megacopta cribraria (Hemiptera: Plataspidae)

The invasive kudzu bug, Megacopta cribraria, was first reported in North America in 2009 and has subsequently spread through most of the southeastern United States, causing yield loss in soybean. Since detection in the USA, research has focused mainly on managing this newly established pest, but many important characteristics of the pest's mouthpart morphology and feeding behavior are unknown. Qualitative and quantitative comparisons of nymph and adult mouthparts and sensilla were made through scanning electron microscopy and light microscopy, and feeding behavior was examined using electropenetrography (EPG) and paraffin histology. Morphologies observed were similar to what has previously been reported for other piercing–sucking hemipterans. The relationship between rostrum length and body size (pronotum width and dorsal length) exhibited negative allometry. Rostrum length exhibited an isometric relationship with interocular width. Adult females (n=9) probed soybean stems 1.3±0.8 times in 9 h, with an average probe time of 2.3±1.3 h. EPG waveforms were characterized and correlated with behavior. Salivary sheaths were shown to terminate in the vascular tissue; four of five sheaths terminated in the phloem. This is the first time that the feeding behavior of a member of the Plataspidae has been recorded using EPG. Results add to our current limited knowledge of plataspid mouthpart morphology and provide a baseline for further research on the feeding behaviors of M. cribraria and other soybean‐feeding hemipterans.     

Immune surveillance properties of human NK cell-derived exosomes

Exosomes are nanovesicles released by normal and tumor cells, which are detectable in cell culture supernatant and human biological fluids, such as plasma. Functions of exosomes released by "normal" cells are not well understood. In fact, several studies have been carried out on exosomes derived from hematopoietic cells, but very little is known about NK cell exosomes, despite the importance of these cells in innate and adaptive immunity. In this paper, we report that resting and activated NK cells, freshly isolated from blood of healthy donors, release exosomes expressing typical protein markers of NK cells and containing killer proteins (i.e., Fas ligand and perforin molecules). These nanovesicles display cytotoxic activity against several tumor cell lines and activated, but not resting, immune cells. We also show that NK-derived exosomes undergo uptake by tumor target cells but not by resting PBMC. Exosomes purified from plasma of healthy donors express NK cell markers, including CD56(+) and perforin, and exert cytotoxic activity against different human tumor target cells and activated immune cells as well. The results of this study propose an important role of NK cell-derived exosomes in immune surveillance and homeostasis. Moreover, this study supports the use of exosomes as an almost perfect example of biomimetic nanovesicles possibly useful in future therapeutic approaches against various diseases, including tumors.     

Identification of amino acid residues critical for the B cell growth-promoting activity of HIV-1 matrix protein p17 variants

Background

HIV-1 matrix protein p17 variants (vp17s) detected in HIV-1-infected patients with non-Hodgkin's lymphoma (HIV-NHL) display, differently from the wild-type protein (refp17), B cell growth-promoting activity. Biophysical analysis revealed that vp17s are destabilized as compared to refp17, motivating us to explore structure-function relationships.

Phenological and aerobiological monitoring of allergenic flora in padua (Italy). Preliminary data

A phenological study on allergenic plants was carried out in Padua during 1995 in order to identify spontaneous and cultivated allergenic species in an urban area and their distribution, and to evaluate the relationship between anthesis length and airborne pollen concentrations. In some cases, there was no temporal overlap between phenological and aerobiological data, in particular forCorylaceae, Betulaceae, Chenopodiaceae, Amaranthaceae, Polygonaceae and Fagaceae.     

Belowground community responses to fire: meta‐analysis reveals contrasting responses of soil microorganisms and mesofauna

Global fire regimes are shifting due to climate and land use changes. Understanding the responses of belowground communities to fire is key to predicting changes in the ecosystem processes they regulate. We conducted a comprehensive meta‐analysis of 1634 observations from 131 empirical studies to investigate the effect of fire on soil microorganisms and mesofauna. Fire had a strong negative effect on soil biota biomass, abundance, richness, evenness, and diversity. Fire reduced microorganism biomass and abundance by up to 96%. Bacteria were more resistant to fire than fungi. Fire reduced nematode abundance by 88% but had no significant effect on soil arthropods. Fire reduced richness, evenness and diversity of soil microorganisms and mesofauna by up to 99%. We found little evidence of temporal trends towards recovery within 10 years post‐disturbance suggesting little resilience of the soil community to fire. Interactions between biome, fire type, and depth explained few of these negative trends. Future research at the intersection of fire ecology and soil biology should aim to integrate soil community structure with the ecosystem processes they mediate under changing global fire regimes.