Dolichodial: A New Aphid Sex Pheromone Component?

The sex pheromones of many aphid species from the subfamily Aphididae comprise a mixture of the iridoids (cyclopentanoids) (1R,4aS,7S,7aR)-nepetalactol and (4aS,7S,7aR)-nepetalactone. In this paper, we investigate whether other chemicals, in addition to nepetalactol and nepetalactone, are released from Dysaphis plantaginea (rosy apple aphid) oviparae as part of their sex pheromone. Four compounds present in an air entrainment sample collected from D. plantaginea oviparae feeding on apple (Malus silvestris c.v. Braburn) elicited electrophysiological responses from male D. plantaginea. Active peaks were tentatively identified by gas chromatography (GC) coupled with mass spectrometry, with identification confirmed by peak enhancement with authentic compounds on GC columns of different polarities. The electroantennography-active chemicals were (1R,4aS,7S,7aR)-nepetalactol, (4aS,7S,7aR)-nepetalactone, (1S,2R,3S)-dolichodial, and phenylacetonitrile. (1S,2R,3S)-Dolichodial elicited a behavioral response from male D. plantaginea and naïve-mated female parasitoids, Aphidius ervi. This is the first report of electrophysiological and behavioral responses from any aphid morph to (1S,2R,3S)-dolichodial. Whether or not (1S,2R,3S)-dolichodial is a third component of the aphid sex pheromone is discussed.     

Tunneling Nanotubes: A New Target for Nanomedicine?

Tunneling nanotubes (TNTs), discovered in 2004, are thin, long protrusions between cells utilized for intercellular transfer and communication. These newly discovered structures have been demonstrated to play a crucial role in homeostasis, but also in the spreading of diseases, infections, and metastases. Gaining much interest in the medical research field, TNTs have been shown to transport nanomedicines (NMeds) between cells. NMeds have been studied thanks to their advantageous features in terms of reduced toxicity of drugs, enhanced solubility, protection of the payload, prolonged release, and more interestingly, cell-targeted delivery. Nevertheless, their transfer between cells via TNTs makes their true fate unknown. If better understood, TNTs could help control NMed delivery. In fact, TNTs can represent the possibility both to improve the biodistribution of NMeds throughout a diseased tissue by increasing their formation, or to minimize their formation to block the transfer of dangerous material. To date, few studies have investigated the interaction between NMeds and TNTs. In this work, we will explain what TNTs are and how they form and then review what has been published regarding their potential use in nanomedicine research. We will highlight possible future approaches to better exploit TNT intercellular communication in the field of nanomedicine.     

Non-Intensive Care Unit Acquired Pneumonia: A New Clinical Entity?

Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP) as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP.     

A New Perspective on Cancer Therapy: Changing the Treaded Path?

During the last decade, we have persistently addressed the question, “how can the innate immune system be used as a therapeutic tool to eliminate cancer?” A cancerous tumor harbors innate immune cells such as macrophages, which are held in the tumor-promoting M2 state by tumor-cell-released cytokines. We have discovered that these tumor-associated macrophages (TAM) are repolarized into the nitric oxide (NO)-generating tumoricidal M1 state by the dietary agent curcumin (CC), which also causes recruitment of activated natural killer (NK) cells and cytotoxic T (Tc) cells into the tumor, thereby eliminating cancer cells as well as cancer stem cells. Indications are that this process may be NO-dependent. Intriguingly, the maximum blood concentration of CC in mice never exceeds nanomolar levels. Thus, our results submit that even low, transient levels of curcumin in vivo are enough to cause repolarization of the TAM and recruitment NK cells as well as Tc cells to eliminate the tumor. We have observed this phenomenon in two cancer models, glioblastoma and cervical cancer. Therefore, this approach may yield a general strategy to fight cancer. Our mechanistic studies have so far implicated induction of STAT-1 in this M2→M1 switch, but further studies are needed to understand the involvement of other factors such as the lipid metabolites resolvins in the CC-evoked anticancer pathways.     

Promotion in Heterogeneous Catalysis: A Topic Requiring a New Approach?

Promoters, and their counterparts poisons, are two topics that have been studied extensively since heterogeneous catalysts have been used industrially. Commercial catalysts tend to involve multiple promoters to enhance the activity, selectivity, lifetime and structural integrity, in addition to guard beds or feedstock purification measures that are used to avoid the adsorption of poisons. Yet, at a fundamental level, there is still considerable debate as to how specific promoters function. Promoter effects tend to be specific to a particular catalyst formulation and generic effects are not common, yet this would be desirable. Generally, in acid catalysis and hydrogenation reactions, promoter effects can be dramatic and unexpected. However, in oxidation reactions of alkanes and alkenes, the promotion effects observed to date are somewhat limited. In this paper, the topic of promotion in heterogeneous catalysis is discussed. The complex interplay between structural and electronic effects of promoters is described using examples of both well defined metal surfaces (e.g., the promoted iron catalyst for ammonia synthesis) and multicrystalline metal, metal oxide and metal phosphate catalysts (e.g., Li-doped MgO for methane oxidation). Subsequently, a molecular approach for the promotion of heterogeneous catalysts is prepared and discussed. This is based on observations from well defined molecular catalysts for homogeneously catalysed processes of ligand accelerated reactions. Examples are described where the effects of ligand acceleration, increasing reaction rate by over two orders of magnitude, can be observed for heterogeneous catalysts for hydrogenation and acid catalysed reactions. The remaining challenge is to identify similar effects for partial oxidation reactions, and it is questioned whether a molecular approach can be developed to meet this challenge.     

Adenovirus Structure: What Is New?

Adenoviruses are large (~950 Å) and complex non-enveloped, dsDNA icosahedral viruses. They have a pseudo-T = 25 triangulation number with at least 12 different proteins composing the virion. These include the major and minor capsid proteins, core proteins, maturation protease, terminal protein, and packaging machinery. Although adenoviruses have been studied for more than 60 years, deciphering their architecture has presented a challenge for structural biology techniques. An outstanding event was the first near-atomic resolution structure of human adenovirus type 5 (HAdV-C5), solved by cryo-electron microscopy (cryo-EM) in 2010. Discovery of new adenovirus types, together with methodological advances in structural biology techniques, in particular cryo-EM, has lately produced a considerable amount of new, high-resolution data on the organization of adenoviruses belonging to different species. In spite of these advances, the organization of the non-icosahedral core is still a great unknown. Nevertheless, alternative techniques such as atomic force microscopy (AFM) are providing interesting glimpses on the role of the core proteins in genome condensation and virion stability. Here we summarize the current knowledge on adenovirus structure, with an emphasis on high-resolution structures obtained since 2010.     

Meropenem–Clavulanate: A New Strategy for the Treatment of Tuberculosis?

The Great White Plague : Mycobacterium tuberculosis, the bacteria causing tuberculosis, is a continuing threat to global health through the emergence of resistant strains and the lack of novel therapeutic agents. Recently reported results on this important work are highlighted.

     

Ozone-Bromine Treatment – Water Treatment in Public Pools without Chlorine: A New Standard?

The central task of the rules and regulations governing water treatment in public swimming pools is to provide guidelines, the compliance with which leads to completely hygienic water. For this purpose, DIN 19643 “Treatment of Water of Swimming Pools and Baths” applies in Germany. To date, this standard has prescribed the chlorination of water. In a therapeutic pool introduced here, water was treated without chlorine. The water quality was observed as part of a long-term study over the course of three years. During the entire period, no germs were detected in the filtrate of the system, not even unspecific CFU germs. The treatment presented here is detailed from both theoretical and practical viewpoints. The treatment uses the oxidation power of ozone to form hypobromous acid as a disinfectant in water containing bromide. A crucial aspect of the treatment is the possible formation of bromate. It is shown that the formation of bromate can be suppressed very effectively. Further bromine-based by-products were monitored. Unpleasant by-products as known from the chlorination were not found. The treatment, known as ozone-bromine Treatment, demonstrates new ways to treat water in public swimming pools and should now be incorporated into the German DIN 19643. It is to be expected that this will also be reflected in the national standards of other countries.     

Inositol (1,4,5)-Trisphosphate Receptors in Invasive Breast Cancer: A New Prognostic Tool?

Simple SummaryThe inositol-trisphosphate receptor (IP₃R) is a key player in physiological and pathological intracellular calcium signaling. The objective of the present study was to assess the putative value of the three IP₃R subtypes as prognostic biomarkers in breast cancer. We found that IP₃R3 is the most strongly expressed subtype in breast cancer tissue. Furthermore, IP₃R3 and IP₃R1 are significantly more expressed in invasive breast cancer tissue than in non-tumor tissue. In contrast to IP₃R1 and IP₃R2, the expression of IP₃R3 was positively correlated with prognostic factors including tumor size, regional node invasion, histologic grade, proliferation index, and hormonal status. By analyzing public databases, we found that the expression of all IP₃R subtypes is significantly correlated with the overall survival and disease-free survival of patients with breast cancer. We conclude that relative to the other two IP₃R subtypes, IP₃R3 expression is upregulated in breast cancer and is correlated with prognostic factors. We strongly believe that our results will open up new perspectives with regard to the link between IP₃Rs and breast cancer aggressiveness.AbstractBreast cancer is the leading cause of cancer death among women in worldwide and France. The disease prognosis and treatment differ from one breast cancer subtype to another, and the disease outcome depends on many prognostic factors. Deregulation of ion flux (especially Ca²⁺ flux) is involved in many pathophysiology processes, including carcinogenesis. Inside the cell, the inositol-trisphosphate receptor (IP₃R) is a major player in the regulation of the Ca²⁺ flux from the endoplasmic reticulum to the cytoplasm. The IP₃Rs (and particularly the IP₃R3 subtype) are known to be involved in proliferation, migration, and invasion processes in breast cancer cell lines. The objective of the present study was to evaluate the potential value of IP₃Rs as prognostic biomarkers in breast cancer. We found that expression levels of IP₃R3 and IP₃R1 (but not IP₃R2) were significantly higher in invasive breast cancer of no special type than in non-tumor tissue from the same patient. However, the IP₃R3 subtype was expressed more strongly than the IP₃R1 and IP₃R2 subtypes. Furthermore, the expression of IP₃R3 (but not of IP₃R1 or IP₃R2) was positively correlated with prognostic factors such as tumor size, regional node invasion, histologic grade, proliferation index, and hormone receptor status. In an analysis of public databases, we found that all IP₃Rs types are significantly associated with overall survival and progression-free survival in patients with breast cancer. We conclude that relative to the other two IP₃R subtypes, IP₃R3 expression is upregulated in breast cancer and is correlated with prognostic factors.     

Threat at One End of the Plant: What Travels to Inform the Other Parts?

Adaptation and response to environmental changes require dynamic and fast information distribution within the plant body. If one part of a plant is exposed to stress, attacked by other organisms or exposed to any other kind of threat, the information travels to neighboring organs and even neighboring plants and activates appropriate responses. The information flow is mediated by fast-traveling small metabolites, hormones, proteins/peptides, RNAs or volatiles. Electric and hydraulic waves also participate in signal propagation. The signaling molecules move from one cell to the neighboring cell, via the plasmodesmata, through the apoplast, within the vascular tissue or—as volatiles—through the air. A threat-specific response in a systemic tissue probably requires a combination of different traveling compounds. The propagating signals must travel over long distances and multiple barriers, and the signal intensity declines with increasing distance. This requires permanent amplification processes, feedback loops and cross-talks among the different traveling molecules and probably a short-term memory, to refresh the propagation process. Recent studies show that volatiles activate defense responses in systemic tissues but also play important roles in the maintenance of the propagation of traveling signals within the plant. The distal organs can respond immediately to the systemic signals or memorize the threat information and respond faster and stronger when they are exposed again to the same or even another threat. Transmission and storage of information is accompanied by loss of specificity about the threat that activated the process. I summarize our knowledge about the proposed long-distance traveling compounds and discuss their possible connections.     

GnRH Antagonists with or without Add-Back Therapy: A New Alternative in the Management of Endometriosis?

To evaluate the effectiveness of a new class of medical drugs, namely oral gonadotropin-releasing hormone (GnRH) antagonists, in the management of premenopausal women with endometriosis-associated pelvic pain. We reviewed the most relevant papers (n = 27) on the efficacy of new medical alternatives (oral GnRH antagonists) as therapy for endometriosis. We first briefly summarized the concept of progesterone resistance and established that oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis. Since clinical evidence shows that estrogens play a critical role in the pathogenesis of the disease, lowering their levels with oral GnRH antagonists may well prove effective, especially in women who fail to respond to progestogens. There is a need for reliable long-term oral treatment capable of managing endometriosis symptoms, taking into consideration both the main symptoms and phenotype of the disease. Published studies reviewed and discussed here confirm the efficacy of GnRH antagonists. There is a place for GnRH antagonists in the management of symptomatic endometriosis. Novel algorithms that take into account the different phenotypes are proposed.     

Astrocytoma: A Hormone-Sensitive Tumor?

Astrocytomas and, in particular, their most severe form, glioblastoma, are the most aggressive primary brain tumors and those with the poorest vital prognosis. Standard treatment only slightly improves patient survival. Therefore, new therapies are needed. Very few risk factors have been clearly identified but many epidemiological studies have reported a higher incidence in men than women with a sex ratio of 1:4. Based on these observations, it has been proposed that the neurosteroids and especially the estrogens found in higher concentrations in women’s brains could, in part, explain this difference. Estrogens can bind to nuclear or membrane receptors and potentially stimulate many different interconnected signaling pathways. The study of these receptors is even more complex since many isoforms are produced from each estrogen receptor encoding gene through alternative promoter usage or splicing, with each of them potentially having a specific role in the cell. The purpose of this review is to discuss recent data supporting the involvement of steroids during gliomagenesis and to focus on the potential neuroprotective role as well as the mechanisms of action of estrogens in gliomas.