Is Hemin Responsible for the Susceptibility of Plasmodia to Oxidant Stress?

Based on the unusually high and stage-dependant susceptibility of Plasmodia to oxidant stress it has been proposed that during parasite development, increasing levels of redox-active forms of iron are gradually released. The purpose of this study was to examine this proposal by using an assay monitoring the levels of available forms of iron for redox reactions. Ascorbate-driven and iron-mediated degradation of adventitious DNA served as the basis for this functional assay.

Incubation of DNA with lysate from infected RBC caused massive degradation, which was dose, time-and parasite-stage dependent. In contrast, lysate from non-infected RBC did not induce DNA degradation. Likewise, lysate only from infected RBC enhanced the aerobic oxidation of ascorbate. These effects on both reactions, DNA degradation and ascorbate oxidation, could be reconstructed with hemin, instead of lysate. Also, chelators exerted similar effects on both reactions.

The results suggest that increased levels of redox-active forms of iron are liberated during parasite development. We propose that hemin or hemin-like structures are the appropriate candidates which could catalyze oxidative stress and deregulate the delicate redox balance of the host-parasite system.     

The Global Burden of Disease Assessments—WHO Is Responsible?

The Global Burden of Disease (GBD) concept has been used by the World Health Organization (WHO) for its reporting on health information for nearly 10 years. The GBD approach results in a single summary measure of morbidity, disability, and mortality, the so-called disability-adjusted life year (DALY). To ensure transparency and objectivity in the derivation of health information, WHO has been urged to use reference groups of external experts to estimate burden of disease. Under the leadership and coordination of WHO, expert groups have been appraising and abstracting burden of disease information. Examples include the Child Health Epidemiology Reference Group (CHERG), the Malaria Monitoring and Evaluation Reference Group (MERG), and the recently established Foodborne Disease Burden Epidemiology Reference Group (FERG). The structure and functioning of and lessons learnt by these groups are described in this paper. External WHO expert groups have provided independent scientific health information while operating under considerable differences in structure and functioning. Although it is not appropriate to devise a single "best practice" model, the common thread described by all groups is the necessity of WHO's leadership and coordination to ensure the provision and dissemination of health information that is to be globally accepted and valued.     

What Component of the Living Cell Is Responsible for Its Semipermeable Properties? Polarized Water or Lipids?

A close correlation (r = +0.96) exists between the permeability (at 0°, 4°, and 25°C) of H₂O and nine other hydroxylic nonelectrolytes through reversed frog skin and through synthetic cellulose-acetate sheets. By the method of least squares, the data yield the following relation: log (P_{frog skin}) = 0.9900 log (P_{cellulose acetate}) -0.1659. Both the reversed frog skin and the cellulose-acetate sheets are semipermeable (while the lipoid membrane is not), showing higher permeability to water than to any other solute used in this series. The data offer support for the theory that it is not lipid, but water polarized in multilayers by cellular proteins, that provides the living cell with its selective surface barrier.     

Is an Apicomplexan Parasite Responsible for the Collapse of the Iceland Scallop (Chlamys islandica) Stock?

Due to the total and unexpected collapse of the Iceland scallop, Chlamys islandica, stocks around Iceland during the 2000s, a commercial fishing ban has been imposed on this valuable resource since 2003. Following the initial identification of an apicomplexan parasite in the scallops, a long-term surveillance program was established to evaluate the effect of the parasite on the population. The infections were highly prevalent in all shell sizes throughout the study. However, the parasite only impacts mature scallops where they cause severe macroscopic changes, characterized by an extensively diminished and abnormally coloured adductor muscle. A highly significant relationship was observed between infection intensity and gonad and adductor muscle indices. The first four years of the study, were characterized by high infection intensity and very poor condition of the adductor muscle and gonads, whilst during subsequent years, infections gradually decreased and the condition of the scallops improved. Histopathological changes were restricted to the presence of apicomplexan zoites which were widely distributed, causing varying degrees of pathology in all organs. In heavy infections, muscular and connective tissues were totally necrotized, destroying significant parts of numerous organs, especially the adductor muscle, digestive gland and gonads. The progression of the disease was in good synchrony with the mortality rates and the subsequent decline observed in the scallop stock and recruitment indices. Our findings strongly suggest that the apicomplexan parasite played a major role in the collapse of the Iceland scallop stock in Breidafjordur. In addition to causing mortality, the infections significantly impact gonad development which contributes further to the collapse of the stock in the form of lower larval recruitment. Furthermore, compelling evidence exists that this apicomplexan pathogen is causing serious disease outbreaks in other scallop populations. Similar abnormal adductor muscles and the parasite itself have been identified or observed in association with other mass mortality events in several different scallop species and commercial stocks in the northern hemisphere.     

Is Growth Hormone Resistance/IGF-1 Reduction Good for You?

GH, IGF-1, and insulin are emerging as important and independent mediators of tumor development and aging. Two recent studies report that humans with GH-receptor deficiency are protected from developing cancer through alterations in GH, IGF-1, and insulin signaling, decreasing the susceptibility of cells to DNA damage and abnormal proliferation.     

Effects of Ambient Particulate Matter on Human Breast Cancer: Is Xenogenesis Responsible?

Background

Recently, evidence from several studies has revealed that air pollution is associated with the increased morbidity and mortality of breast cancer patients. However, to date, the underlying mechanism remains largely unclear. Considering the high prevalence of air pollution and breast cancer in China, it is necessary to understand how air pollution may affect breast cancer.

Methods

We analyzed 1,832 female patients who had resided in the same cities for at least 10 years prior to their diagnosis. Variables including demographic data as well as clinical and tumor characteristics, including the patient’s age at menarche, family history of breast cancer, tumor histopathological type, tumor size, lymph node metastasis, distant metastasis, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER-2) status at the time of diagnosis were analyzed.

Results

Compared to patients residing in low-pollution areas, patients living in high-pollution areas demonstrated a younger age at menarche (p<0.001), a greater family history of breast cancer (p = 0.034) and more invasive cancers (p = 0.028) with higher tumor grades (p = 0.028) and estrogen receptor (ER)-positive status (p = 0.022). Differences in tumor grade were only found in ER-positive cases.

Conclusions

Our findings and clinical data indicate that long-term air pollution exposure may contribute to the development of breast cancer by playing the role of a xenoestrogen, and also provides new insight into the association between air pollution and the morbidity and mortality of breast cancer patients. Furthermore, it is urgently necessary to study the association between air pollution and breast cancer to improve the living quality and health of females, and applicable public health strategies may need to be established or modified as soon as possible.     

Invasive meningococcal disease and latex agglutination test — Is it still beneficial for diagnosis?

We showed current clinical usefulness of the latex agglutination (LA) test for confirmation of meningococcal etiology on 32 cerebrospinal fluid, 77 serum and 93 urine samples collected during the first week of hospitalization from 19 patients with laboratory confirmed invasive meningococcal disease. The positivity of the LA test in cerebrospinal fluid was 47%, in serum 42% and in urine 24%, while the PCR of cerebrospinal fluid and serum was positive in 95 and 47% cases, respectively. The latest positivity of the LA test was detected on day 2 in cerebrospinal fluid, on day 3 in serum and on day 4 in urine. In the group of patients who had received antibiotic therapy we found nonsignificant reduction of LA positivity and also statistically significant reduction of culture positivity in CSF (p = 0.04); the PCR positivity changed minimally. In blood samples, nonsignificant reduction of culture positivity and no difference in LA and PCR positivity was found. We did not find any statistically significant relationship between test results and clinical forms. The LA test can be therefore considered to be an auxiliary diagnostic method, rapid and easily practicable but less sensitive than PCR. It can be recommended especially for local laboratories where PCR is not available and the patient already received antibiotics before admission to the hospital.     

Investigation of Tissue Preparation Conditions for Non-radioactive In Situ Hybridization: Localization of Transforming Growth Factor-α Message in Rat Kidney

A non-radioactive method of in situ hybridization was used to localize transforming growth factor- mRNA in epithelial cells of collecting ducts and tubules in rat kidney tissue sections. The intensity and specificity of staining were assessed under a variety of tissue preparation conditions, including a direct comparison of paraffin against frozen sections. Under optimal conditions, both the signal strength and the cellular localization of the growth factor message were superior in paraffin sections. The staining method could also be used to localize the message in lung tissue, indicating that the procedure is generally applicable to other tissues. Our results indicate that the use of paraffin sections for non-radioactive in situ hybridization affords a number of advantages for the localization of specific messages in tissue sections.     

Is Physiological Performance a Good Predictor for Fitness? Insights from an Invasive Plant Species

Is physiological performance a suitable proxy of fitness in plants? Although, several studies have been conducted to measure some fitness-related traits and physiological performance, direct assessments are seldom found in the literature. Here, we assessed the physiology-fitness relationship using second-generation individuals of the invasive plant species Taraxacum officinale from 17 localities distributed in five continents. Specifically, we tested if i) the maximum quantum yield is a good predictor for seed-output ii) whether this physiology-fitness relationship can be modified by environmental heterogeneity, and iii) if this relationship has an adaptive consequence for T. officinale individuals from different localities. Overall, we found a significant positive relationship between the maximum quantum yield and fitness for all localities evaluated, but this relationship decreased in T. officinale individuals from localities with greater environmental heterogeneity. Finally, we found that those individuals from localities where environmental conditions are highly seasonal performed better under heterogeneous environmental conditions. Contrarily, under homogeneous controlled conditions, those individuals from localities with low environmental seasonality performed much better. In conclusion, our results suggest that the maximum quantum yield seem to be good predictors for plant fitness. We suggest that rapid measurements, such as those obtained from the maximum quantum yield, could provide a straightforward proxy of individual’s fitness in changing environments.     

The GPIHBP1–LPL Complex Is Responsible for the Margination of Triglyceride-Rich Lipoproteins in Capillaries

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Is Ffh required for export of secretory proteins?

In Escherichia coli, protein export from the cytoplasm may occur via the signal recognition particle (SRP)-dependent pathway or the Sec-dependent pathway. Membrane proteins utilize the SRP-dependent route, whereas many secretory proteins use the cytoplasmic Sec machinery. To examine the possibility that signal peptide hydrophobicity governs which targeting route is utilized, we used a series of PhoA signal sequence mutants which vary only by incremental hydrophobicity changes. We show that depletion of SRP, but not trigger factor, affects all the mutants examined. These results suggest secretory proteins with a variety of signal sequences, as well as membrane proteins, require SRP for export.     

Are Echinocandins Better Than Azoles for Invasive Candidiasis?

Antifungal therapy has advanced tremendously in the past decade, with multiple new agents for systemic fungal infections that have a broad spectrum of activity and are well-tolerated. There is usually more than one acceptable therapeutic option for many diseases, and this is true in particular of candidiasis. Fluconazole has been the drug of choice for most clinical syndromes of candidiasis, due to its tolerability, effectiveness, and ease of administration. However, the echinocandin class of antifungals, comprised of caspofungin, micafungin and anidulafingin, has emerged as the preferred choice in the therapy of invasive candidiasis and candidemia. Their potent fungicidal activity and minimal toxicity have made them first-line drugs for this indication. In certain clinical settings, they may even be agents of first choice. Nevertheless, recent trends in echinocandin resistance demonstrated with Candida glabrata mandate ongoing surveillance, and continued trends may impact upon future antifungal selection.     

βKlotho Is Required for Fibroblast Growth Factor 21 Effects on Growth and Metabolism

Fibroblast growth factor 21 (FGF21) is a fasting-induced hepatokine that has potent pharmacologic effects in mice, which include improving insulin sensitivity and blunting growth. The single-transmembrane protein βKlotho functions as a coreceptor for FGF21 in?vitro. To determine if βKlotho is required for FGF21 action in?vivo, we generated whole-body and adipose tissue-selective βKlotho-knockout mice. All of the effects of FGF21 on growth and metabolism were lost in whole-body βKlotho-knockout mice. Selective elimination of βKlotho in adipose tissue blocked the acute insulin-sensitizing effects of FGF21. Taken together, these data demonstrate that βKlotho is essential for FGF21 activity and that βKlotho in adipose tissue contributes to the beneficial metabolic actions of FGF21.     

Evaluation of MycAssay? Aspergillus for Diagnosis of Invasive Pulmonary Aspergillosis in Patients without Hematological Cancer

Methods based on real-time polymerase chain reaction (PCR) can speed up the diagnosis of invasive aspergillosis but are limited by a lack of standardization. We evaluated the commercially available MycAssay™ Aspergillus test for the diagnosis of invasive aspergillosis in patients without hematological cancer. We prospectively collected 322 lower respiratory tract samples (November 2009–January 2011) from 175 patients with lower respiratory tract infection and the following predisposing conditions: solid cancer (16.8%), cirrhosis (16.8%), corticosteroid therapy (71.7%), HIV infection (15.6%), chronic obstructive pulmonary disease (COPD, 52.6%), solid organ transplantation (kidney [1.2%], heart [3%], liver [4.6%]), or none (3.5%). Specimens were obtained when clinically indicated and analyzed in the microbiology laboratory. Aspergillus DNA was extracted and amplified by means of MycXtra® and MycAssay™ Aspergillus. Aspergillus spp. was isolated from 65 samples (31 patients). According to the European Organization for Research and Treatment of Cancer and Bulpa''s criteria (for patients with COPD), 15 had probable invasive aspergillosis. MycAssay™ Aspergillus results were negative (n = 254), positive (n = 54), or indeterminate (n = 14). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio of the MycAssay™ (first sample/any sample) were 86.7/93, 87.6/82.4, 34.1/34.1, 92.2/100, and 48/68.75. The differences between the proportion of samples with positive PCR determinations (63%) and the proportion of samples with Aspergillus spp. isolation (75%) did not reach statistical significance (P = 0.112). The median time from sample culture to visualization of fungal growth was 3 days, compared with ∼4 hours for MycAssay™ Aspergillus PCR. MycAssay™ Aspergillus showed high sensitivity for the diagnosis of invasive aspergillosis in patients without hematological cancer. Sensitivity increased when multiple samples were used. Compared with fungal culture, PCR significantly reduced the time to diagnosis.