CD34+ leukemic subpopulation predominantly displays lower spontaneous apoptosis and has higher expression levels of Bcl-2 and MDR1 genes than CD34− cells in childhood AML

In view of obscure clinical and biological significance of leukemic cells heterogeneity, we studied the efficacy of apoptosis, proliferation, and expression levels of the Bcl-2, MDR1, LRP, and BCRP genes in sorted CD34+ and CD34− subpopulations of childhood AML leukemic samples. In five out of nine cases, CD34+ cells were less sensitive to spontaneous apoptosis and had from 1.2- to 5.0-fold higher expression levels of Bcl-2 (eight of ten) and from 1.5- to 28.7-fold higher expression levels of MDR1 (eight of ten). The expression levels of the LRP gene were from 1.1- to 1.8-fold higher in CD34+ subpopulations (five of ten cases), and the expression levels of the BCRP gene were from 1.1- to 22.4-fold higher in CD34+ leukemic cells (six of ten). In all M4 cases, the expression levels of LRP were higher in the CD34− subpopulation. Significant differences in the patterns of genes expression between patients do not allow us to conclude that the CD34+ fractions have more resistant phenotype than the CD34− subpopulations. Nevertheless, distinctions between CD34+ and CD34− cells may lead to different chemosensitivities between leukemic subpopulations in vivo and may determine the alteration of the leukemic immunophenotype during treatment and in relapse.     

Optimising care of patients with chronic disease: patient‐oriented education may improve disease knowledge and self‐management

Many patients with chronic disease do not possess the knowledge and skills required to access and interpret appropriate health information. A pilot study in people with liver cirrhosis (n = 50) identified that only 54% of patients could recall being given written information by a clinician and 64% had self‐sought information, most commonly using the Internet. Many patients reported difficulties understanding the material and the majority wanted more accessible information. A pilot chronic disease educational booklet was well received by the study participants with 85% reporting it was helpful and 78% using it in between clinic appointments.     

Cellular mechanisms of motor control in the vibrissal system

In this article we discuss the experimental advantages that the vibrissal motor system offers for analysis of motor control and the specializations of this system related to the unique characteristics of whisker movements. Whisker movements are often rhythmic, fast, and bilateral. Movements of individual whiskers have simple characteristics, whereas, movements of the entire vibrissae array are complex and sophisticated. In the last few years, powerful methods for high precision tracking of whisker movements have become available. The whisker musculature is arranged to permit forward movements of individual whiskers and consists—depending on the species—mainly or exclusively of fast contracting, fast fatigable muscle fibers. Whisker motor neurons are located in the lateral facial nucleus and their cellular properties might contribute to the rhythmicity of whisking. Numerous structures provide input to the lateral facial nucleus, the most mysterious and important one being the putative central pattern generator (CPG). Although recent studies identified candidate structures for the CPG, the precise identity and the functional organization of this structure remains uncertain. The vibrissa motor cortex (VMC) is the largest motor representation in the rodent brain, and recent work has clarified its localization, subdivisions, cytoarchitectonics, and connectivity. Single-cell stimulation experiments in VMC allow determining the cellular basis of cortical motor control with unprecedented precision. The functional significance of whisker movements remains to be determined.     

Mesenchymal stem cell adhesion and spreading on microwave plasma-nitrided titanium alloy

Improved methods to increase surface hardness of metallic biomedical implants are being developed in an effort to minimize the formation of wear debris particles that cause local pain and inflammation. However, for many implant surface treatments, there is a risk of film delamination due to the mismatch of mechanical properties between the hard surface and the softer underlying metal. In this article, we describe the surface modification of titanium alloy (Ti-6Al-4V), using microwave plasma chemical vapor deposition to induce titanium nitride formation by nitrogen diffusion. The result is a gradual transition from a titanium nitride surface to the bulk titanium alloy, without a sharp interface that could otherwise lead to delamination. We demonstrate that vitronectin adsorption, as well as the adhesion and spreading of human mesenchymal stem cells to plasma-nitrided titanium is equivalent to that of Ti-6Al-4V, while hardness is improved 3- to 4-fold. These in vitro results suggest that the plasma nitriding technique has the potential to reduce wear, and the resulting debris particle release, of biomedical implants without compromising osseointegration; thus, minimizing the possibility of implant loosening over time.     

Docosahexanoic acid antagonizes TNF-α-induced necroptosis by attenuating oxidative stress,ceramide production,lysosomal dysfunction,and autophagic features

Objective

It was previously reported that docosahexanoic acid (DHA) reduces TNF-α-induced necrosis in L929 cells. However, the mechanisms underlying this reduction have not been investigated. The present study was designed to investigate cellular and biochemical mechanisms underlying the attenuation of TNF-α-induced necroptosis by DHA in L929 cells.

Methods

L929 cells were pre-treated with DHA prior to exposure to TNF-α, zVAD, or Necrostatin-1 (Nec-1). Cell death and survival were assessed by MTT and caspase activity assays, and microscopic visualization. Reactive oxygen species (ROS) were measured by flow cytometry. C16- and C18-ceramides were measured by mass spectrometry. Lysosomal membrane permeabilization (LMP) was evaluated by fluorescence microscopy and flow cytometry using Acridine Orange. Cathepsin L activation was evaluated by immunoblotting and fluorescence microscopy. Autophagy was assessed by immunoblotting of LC3-II and Beclin.

Results

Exposure of L929 cells to TNF-α alone for 24 h induced necroptosis, as evidenced by the inhibition of cell death by Nec-1, absence of caspase-3 activity and Lamin B cleavage, and morphological analysis. DHA attenuated multiple biochemical events associated with TNF-α-induced necroptosis, including ROS generation, ceramide production, lysosomal dysfunction, cathepsin L activation, and autophagic features. DHA also attenuated zVAD-induced necroptosis but did not attenuate the enhanced apoptosis and necrosis induced by the combination of TNF-α with Actinomycin D or zVAD, respectively, suggesting that its protective effects might be limited by the strength of the cell death insult induced by TNF-α.

Conclusions

DHA effectively attenuates TNF-α-induced necroptosis and autophagy, most likely via its ability to inhibit TNF-α-induced sphingolipid metabolism and oxidative stress. These results highlight the role of this Omega-3 fatty acid in antagonizing inflammatory cell death.     

New species and records of the mite genus Prolistrophorus (Acariformes: Listrophoridae) from rodents of the subfamily Sigmodontinae (Rodentia: Cricetidae)

Six fur-mite species of the genus Prolistrophorus Fain, 1970 (Acariformes: Listrophoridae) were recorded from Central and South American rodents of the subfamily Sigmodontinae (Rodentia: Cricetidae). Among them, Prolistrophorus (Aprolistrophorus) parabidentatus sp. nov. from Akodon azarae from Argentina and Prolistrophorus (Aprolistrophorus) tylomys sp. nov. from Tylomys nudicaudus from Guatemala are described as new for science. New hosts are recorded for the following species: Prolistrophorus (Prolistrophorus) grassii (Radford, 1954) from Zygodontomys brevicauda from Colombia, P. (P.) frontalis (Hirst, 1921) from Oligoryzomys sp. from Argentina, P. (P.) argentinus (Hirst, 1921) from Melanomys caliginosus, Akodon affinis from Colombia and Scapteromys aquaticus from Argentina, Prolistrophorus (Beprolistrophorus) hirstianus Fain, 1973 from Scapteromys aquaticus from Argentina.     

Rhinovirus species and clinical characteristics in the first wheezing episode in children

The clinical data on the first wheezing episodes induced by different rhinovirus (RV) species are still limited. We aimed to investigate the prevalence of RV genotypes, sensitization status, and clinical characteristics of patients having a respiratory infection caused by either different RV species or other respiratory viruses. The study enrolled 111 patients (aged 3–23 months, 79% hospitalized, 76% with RV infection) with the first wheezing episode. RV‐specific sequences were identified by partial sequencing of VP4/VP2 and 5′ non‐coding regions with 80% success rate. The investigated clinical and laboratory variables included atopic characteristics and illness severity, parental atopic illnesses, and parental smoking. Of the study children, 56% percent had > 1 atopic characteristic (atopy, eczema and/or blood eosinophil count > 0.4 × 10⁹/L) and 23% were sensitised to allergens. RV‐C was detected in 58% of RV positive samples, followed by RV‐A (20%) and RV‐B (1.2%). Children with RV‐A and RV‐C induced wheezing were older (P = 0.014) and had more atopic characteristics (P = 0.001) than those with non‐RV. RV‐A and RV‐C illnesses had shorter duration of preadmission symptoms and required more bronchodilator use at the ward than non‐RV illnesses (both P < 0.05, respectively). RV‐C is the most common cause of severe early wheezing. Atopic and illness severity features are associated with children having RV‐A or RV‐C induced first wheezing episode rather than with children having a non‐RV induced wheezing. J. Med. Virol. 88:2059–2068, 2016. © 2016 Wiley Periodicals, Inc.