Pallial origin of basal forebrain cholinergic neurons in the nucleus basalis of Meynert and horizontal limb of the diagonal band nucleus

The majority of the cortical cholinergic innervation implicated in attention and memory originates in the nucleus basalis of Meynert and in the horizontal limb of the diagonal band nucleus of the basal prosencephalon. Functional alterations in this system give rise to neuropsychiatric disorders as well as to the cognitive alterations described in Parkinson and Alzheimer's diseases. Despite the functional importance of these basal forebrain cholinergic neurons very little is known about their origin and development. Previous studies suggest that they originate in the medial ganglionic eminence of the telencephalic subpallium; however, our results identified Tbr1-expressing, reelin-positive neurons migrating from the ventral pallium to the subpallium that differentiate into cholinergic neurons in the basal forebrain nuclei projecting to the cortex. Experiments with Tbr1 knockout mice, which lack ventropallial structures, confirmed the pallial origin of cholinergic neurons in Meynert and horizontal diagonal band nuclei. Also, we demonstrate that Fgf8 signaling in the telencephalic midline attracts these neurons from the pallium to follow a tangential migratory route towards the basal forebrain.     

Snapping magnetosome chains by asymmetric cell division in magnetotactic bacteria

The mechanism by which prokaryotic cells organize and segregate their intracellular organelles during cell division has recently been the subject of substantial interest. Unlike other microorganisms, magnetotactic bacteria (MTB) form internal magnets (known as magnetosome chain) for magnetic orientation, and thus face an additional challenge of dividing and equipartitioning this magnetic receptor to their daughter cells. Although MTB have been investigated more than four decades, it is only recently that the basic mechanism of how MTB divide and segregate their magnetic organelles has been addressed. In this issue of Molecular Microbiology, the cell cycle of the model magnetotactic bacterium, Magnetospirillum gryphiswaldense is characterized by Katzmann and co-workers. The authors have found that M. gryphiswaldense undergoes an asymmetric cell division along two planes. A novel wedge-like type of cellular constriction is observed before separation of daughter cells and magnetosome chains, which is assumed to help cell cope with the magnetic force within the magnetosome chain. The data shows that the magnetosome chain becomes actively recruited to the cellular division site, in agreement with the previous suggestions described by Staniland et al. (2010), and the actin-like protein MamK is likely involved in this fast polar-to-midcell translocalization. With the use of cryo-electron tomography, an arc-shaped Z ring is observed near the division site, which is assumed to trigger the asymmetric septation of cell and magnetosome chain.     

Gene detection of staphylococcal enterotoxins in production strain of staphylococcin injection and superantigenic activity of rSEK and rSEQ

In China, staphylococcin injection has been commonly used in the combined treatment of cancer to enhance the systemic immune response and reduce the toxicities associated with chemotherapy and radiation therapy. It is claimed that the main active component in the injection is staphylococcal enterotoxin C2 (SEC2). To determine whether other serological types of staphylococcal enterotoxins (SEs) could also be present in the injection products, in this study, the distribution of se genes (from sea to see, from seg to seu) in the one and only production strain of Staphylococcus aureus from one manufacturing company was analyzed by PCR method. In addition, sek and seq genes were cloned from the strain and the corresponding recombinant proteins, rSEK and rSEQ, were expressed in Escherichia coli and purified by affinity chromatography and anion-exchange chromatography. The superantigenic properties of the two recombinant proteins were then measured by MTT method. The PCR results showed that seven se genes are harbored by the production strain. However, sec2 gene was not detected. The results of MTT assay showed that rSEK and rSEQ could elicit strong stimulatory effects on proliferation and cytotoxicity of murine splenocytes in vitro. Overall, the results in this study indicated that one or a plurality of the seven SEs may be present in the related products, and that the two recombinant SEs are promising candidates as immunomodulatory agents for cancer therapy.     

Simultaneous detection of dual proteins using quantum dots coated silica nanoparticles as labels

Simultaneous detection of multianalytes associated with a particular cancer is beneficial for disease diagnosis. Here, a facile immunosensing strategy was designed to allow simultaneous electrochemical detection of dual proteins, in a single run. CdSe and PbS water-soluble quantum dots (QDs) were prepared and coated on monodisperse silica nanoparticles as labels for proteins detection. Rabbit immunoglobulin G antigen (IgG) and carcinoembryonic antigen (CEA) were chosen as model proteins for analysis. After a typical sandwich immunoassay, CdSe and PbS QDs labels were introduced onto the Au substrates' surface, which were then dissolved and could be simultaneously monitored by square-wave-voltammetric (SWV) stripping measurements. Under selected conditions, IgG and CEA could be assayed in the ranges of 0.05-40 ng mL(-1) and 0.05-25 ng mL(-1), respectively. The proposed method possessed high sensitivity, good precision, and satisfactory reproducibility and regeneration.     

Mix and match: heterodimers and opioid tolerance

The mechanism by which multiple brain structures interact to support working memory is not yet fully understood. In this issue of Neuron, Fujisawa and Buzsáki report that coordinated oscillatory activities between the hippocampus, prefrontal cortex, and ventral tegmental area (VTA) may be a key neural correlate of working memory.     

The effect of feed salinity on the biofouling dynamics of seawater desalination

A persistent cell labeling dye and a novel microbial counting method were used to explore the effects of salinity on a microbial population in a reverse osmosis (RO) desalination system, and these clearly distinguished microbial cell multiplication from cell adherence. The results indicated that microbial multiplication is more active at the front of a seawater RO pressure vessel, while adhesion dominates the back of the vessel. A severe reduction in RO permeate flux and total dissolved solid (TDS) rejection were detected at low salinity, attributed to marked cell multiplication and release of extracellular polymeric substances, whilst a relatively stable flux was observed at medium and high salinity. The results from PCR-DGGE revealed the variation in microbial species distribution on the membrane with salinity. The results imply the critical role of membrane modification in biofouling mitigation in the desalination process.     

Up-regulation of the novel proinflammatory adipokines lipocalin-2, chitinase-3 like-1 and osteopontin as well as angiogenic-related factors in visceral adipose tissue of patients with colon cancer

Background

Obesity is widely recognised as an important risk factor for colorectal cancer (CC).

Aim

The study aimed to evaluate the effect of CC on circulating concentrations and gene expression levels of inflammatory and angiogenesis-related factors in human visceral adipose tissue (VAT).

Methods

VAT biopsies were obtained from 18 healthy individuals and 11 patients with CC. Real-time polymerase chain reactions were performed to quantify gene expression levels and zymographic analyses were used to determine the activity of matrix metalloproteinases (MMPs).

Results

Patients with CC exhibited increased mRNA expression levels of lipocalin-2 (P=.014), osteopontin (P=.027), tumor necrosis factor-α (TNF-α) (P=.016) and chitinase-3 like-1 (P=.006) compared to control subjects in VAT. Gene expression levels of hypoxia-inducible factor-1 α, vascular endothelial growth factor and MMP-2 were significantly higher (P<.05) in VAT of patients with CC. The expression of insulin-like growth factor I, insulin growth factor binding protein 3 and MMP-9 followed the same trend, although no significant differences were reached. The enzymatic activity of MMP-9 was increased (P<.001) in patients with CC. Furthermore, individuals with CC showed increased (P<.05) circulating concentrations of the inflammatory markers interleukin-6, tumour necrosis factor α and hepatocyte growth factor, whereas levels of the anti-inflammatory adipokine adiponectin were decreased (P<.01).

Conclusion

These findings represent the first observation that mRNA levels of the novel inflammatory factors lipocalin-2, chitinase-3 like-1 and osteopontin are increased in human VAT of subjects with CC. This observation together with the up-regulation of angiogenic factors suggests that adipokines secreted by VAT may be involved in the development of colon cancer.     

Combination of arsenic trioxide and BCNU synergistically triggers redox-mediated autophagic cell death in human solid tumors

Arsenic trioxide (As₂O₃) is an effective treatment for relapsed or refractory acute promyelocytic leukemia (APL). After the discovery of As₂O₃ as a promising treatment for APL, several studies investigated the use of As₂O₃ as a single agent in the treatment of solid tumors; however, its therapeutic efficacy is limited. Thus, the systematic study of the combination of As₂O₃ with other clinically used chemotherapeutic drugs to improve its therapeutic efficacy in treating human solid tumors is merited. In this study, we demonstrate for the first time, using isobologram analysis, that As₂O₃ exhibits a synergistic interaction with N,N′-bis(2-chloroethyl)-N-nitrosourea (BCNU). The synergistic augmentation of the cytotoxicity of As₂O₃ with BCNU is in part through the autophagic cell death machinery in human solid tumor cells. As₂O₃ and BCNU in combination produce enhanced cytotoxicity via the depletion of reduced glutathione (GSH) and augmentation of reaction oxygen species (ROS) production. Further analysis indicated that the extension of GSH depletion by this combined regimen occurs through the inhibition of the catalytic activity of glutathione reductase. Blocking ROS production with antioxidants or ROS scavengers effectively inhibits cell death and autophagy formation, indicating that redox-mediated autophagic cell death involves the synergism of As₂O₃ with BCNU. Taken together, this is the first evidence that BCNU could help to extend the therapeutic spectrum of As₂O₃. These findings will be useful in designing future clinical trials of combination chemotherapy with As₂O₃ and BCNU, with the potential for broad use against a variety of solid tumors.