Comparative neuroanatomy suggests repeated reduction of neuroarchitectural complexity in Annelida

Background

Paired mushroom bodies, an unpaired central complex, and bilaterally arranged clusters of olfactory glomeruli are among the most distinctive components of arthropod neuroarchitecture. Mushroom body neuropils, unpaired midline neuropils, and olfactory glomeruli also occur in the brains of some polychaete annelids, showing varying degrees of morphological similarity to their arthropod counterparts. Attempts to elucidate the evolutionary origin of these neuropils and to deduce an ancestral ground pattern of annelid cerebral complexity are impeded by the incomplete knowledge of annelid phylogeny and by a lack of comparative neuroanatomical data for this group. The present account aims to provide new morphological data for a broad range of annelid taxa in order to trace the occurrence and variability of higher brain centers in segmented worms.

Results

Immunohistochemically stained preparations provide comparative neuroanatomical data for representatives from 22 annelid species. The most prominent neuropil structures to be encountered in the annelid brain are the paired mushroom bodies that occur in a number of polychaete taxa. Mushroom bodies can in some cases be demonstrated to be closely associated with clusters of spheroid neuropils reminiscent of arthropod olfactory glomeruli. Less distinctive subcompartments of the annelid brain are unpaired midline neuropils that bear a remote resemblance to similar components in the arthropod brain. The occurrence of higher brain centers such as mushroom bodies, olfactory glomeruli, and unpaired midline neuropils seems to be restricted to errant polychaetes.

Conclusions

The implications of an assumed homology between annelid and arthropod mushroom bodies are discussed in light of the 'new animal phylogeny'. It is concluded that the apparent homology of mushroom bodies in distantly related groups has to be interpreted as a plesiomorphy, pointing towards a considerably complex neuroarchitecture inherited from the last common ancestor, Urbilateria. Within the annelid radiation, the lack of mushroom bodies in certain groups is explained by widespread secondary reductions owing to selective pressures unfavorable for the differentiation of elaborate brains. Evolutionary pathways of mushroom body neuropils in errant polychaetes remain enigmatic.     

Symptomatic relief precedes improvement of myocardial blood flow in patients under spinal cord stimulation

Background

Spinal cord electrical stimulation (SCS) has shown to be a treatment option for patients suffering from angina pectoris CCS III-IV although being on optimal medication and not suitable for conventional treatment strategies, e.g. CABG or PTCA. Although many studies demonstrated a clear symptomatic relief under SCS therapy, there are only a few short-term studies that investigated alterations in cardiac ischemia. Therefore doubts remain whether SCS has a direct effect on myocardial perfusion.

Methods

A prospective study to investigate the short- and long-term effect of spinal cord stimulation (SCS) on myocardial ischemia in patients with refractory angina pectoris and coronary multivessel disease was designed. Myocardial ischemia was measured by MIBI-SPECT scintigraphy 3 months and 12 months after the beginning of neurostimulation. To further examine the relation between cardiac perfusion and functional status of the patients we measured exercise capacity (bicycle ergometry and 6-minute walk test), symptoms and quality of life (Seattle Angina Questionnaire [SAQ]), as well.

Results

31 patients (65 ± 11 SEM years; 25 male, 6 female) were included into the study. The average consumption of short acting nitrates (SAN) decreased rapidly from 12 ± 1.6 times to 3 ± 1 times per week. The walking distance and the maximum workload increased from 143 ± 22 to 225 ± 24 meters and 68 ± 7 to 96 ± 12 watt after 3 months. Quality of life increased (SAQ) significantly after 3 month compared to baseline, as well. No further improvement was observed after one year of treament. Despite the symptomatic relief and the improvement in maximal workload computer based analysis (Emory Cardiac Toolbox) of the MIBI-SPECT studies after 3 months of treatment did not show significant alterations of myocardial ischemia compared to baseline (16 patients idem, 7 with increase and 6 with decrease of ischemia, 2 patients dropped out during initial test phase). Interestingly, in the long-term follow up after one year 16 patients (of 27 who completed the one year follow up) showed a clear decrease of myocardial ischemia and only one patient still had an increase of ischemia compared to baseline.

Conclusion

Thus, spinal cord stimulation not only relieves symptoms, but reduces myocardial ischemia as well. However, since improvement in symptoms and exercise capacity starts much earlier, decreased myocardial ischemia might not be a direct effect of neurostimulation but rather be due to a better coronary collateralisation because of an enhanced physical activity of the patients.     

Subcutaneous Bortezomib in Multiple Myeloma Patients Induces Similar Therapeutic Response Rates as Intravenous Application But It Does Not Reduce the Incidence of Peripheral Neuropathy

Objective

Subcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration.

Patients and methods

During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly – 63% or twice weekly – 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.

Results

The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥2 was present in 20% vs 18% and PN grade ≥3 was present in 6% vs 4%.

Conclusions

We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.     

Ordovician radiolaria and conodonts from the peri-Gondwanan Karatau-Naryn microplate (Sarydzhaz, eastern Kyrgyzstan)

Cambrian-Ordovician sedimentary sequences crop out extensively in the area surrounding the Sarydzhaz River, a remote mountainous region situated in the eastern part of Kyrgyzstan. These sequences, composed essentially of fine siliciclastic lithologies, were deposited on a passive margin of the peri-Gondwanan Karatau-Naryn microplate. Palaeontological constraints for the age of these sequences are rare. Recent efforts of geological mapping in the area discovered reasonably well-preserved radiolarian and conodont faunas. The occurrence of conodonts was mentioned previously, but no taxonomic details were ever reported. Two conodont assemblages are identified from the Oldzhobai Formation; the first is dominated by Paracordylodus gracilis, which can be correlated with the upper Tremadocian to lower Floian; the second assemblage is more diverse and characterized by Prioniodus elegans, suggesting a mid Floian age. This is the first discovery of Ordovician Radiolaria from Kyrgyzstan. In spite of its rather moderately good to poor preservation, the fauna is interesting in many respects, especially due to the presence of a new radiolarian species (Inanigutta (?) kyrgyza nov. sp.). The latter is easily identifiable by the distinctive pore pattern of its cortical shell and has therefore the potential to become in the future a biostratigraphic marker species.     

MicroRNAs in cancer drug resistance: Basic evidence and clinical applications

Development of drug resistance has considerably limited the efficacy of cancer treatments, including chemotherapy and targeted therapies. Hence, understanding the molecular mechanisms underpinning the innate or the acquired resistance to these therapies is critical to improve drug efficiency and clinical outcomes. Several studies have implicated microRNAs (miRNA) in this process. MiRNAs repress gene expression by specific binding to complementary sequences in the 3' region of target messenger RNAs (mRNAs), followed by target mRNA degradation or blocked translation. By targeting molecules specific to a particular pathway within tumor cells, the new generation of cancer treatment strategies has shown significant advantages over conventional chemotherapy. However, the long-term efficacy of targeted therapies often remains poor, because tumor cells develop resistance to such therapeutics. Targeted therapies often involve monoclonal antibodies (mAbs), such as those blocking the ErB/HER tyrosine kinases, epidermal growth factor receptor (cetuximab) and HER2 (trastuzumab), and those inhibiting vascular endothelial growth factor receptor signaling (e.g., bevacizumab). Even though these are among the most used agents in tumor medicine, clinical response to these drugs is reduced due to the emergence of drug resistance as a result of toxic effects in the tumor microenvironment. Research on different types of human cancers has revealed that aberrant expression of miRNAs promotes resistance to the aforementioned drugs. In this study, we review the mechanisms of tumor cell resistance to mAb therapies and the role of miRNAs therein. Emerging treatment strategies combine therapies using innovative miRNA mimics or antagonizers with conventional approaches to maximize outcomes of patients with cancer.     

In silico Analysis of Different Signal Peptides for the Excretory Production of Recombinant NS3-GP96 Fusion Protein in Escherichia coli

International Journal of Peptide Research and Therapeutics - Escherichia coli is one of the simplest hosts which is widely being used to express heterologous proteins. However, without appropriate...     

Body Mass Index Development from Birth to Early Adolescence; Effect of Perinatal Characteristics and Maternal Migration Background in a Swedish Cohort

Background

Well documented diversity in risk of developing overweight and obesity between children of immigrant and of native mothers, might be explained by different body mass index (BMI) development trajectories in relation to maternal and perinatal characteristics of offspring.

Objectives

To assess BMI development trajectories among children born to immigrant and to Swedish mothers from birth to adolescence in relation to perinatal characteristics.

Methods

A cohort of 2517 children born in Stockholm during 1994 to 1996 was followed with repeated measurement of height and weight at eleven time points until age 12 years. We estimated changes over time for BMI in relation to maternal and perinatal characteristics of offspring using mixed linear model analysis for repeated measure data.

Results

We observed a significant BMI change over time in children and time interaction with maternal migration status (P<0.0001). Estimated BMI over time adjusted for maternal and perinatal characteristics of offspring, showed slower BMI growth before age of 5, followed by an earlier plateau and steeper BMI growth after 5 years among children of immigrant mothers compared with children of Swedish mothers. These differences in BMI growth were more prominent among children with mothers from outside Europe.

Conclusion

Beside reinforcing early childhood as a crucial period in development of overweight, the observed slower BMI development at early childhood among children of immigrants followed by a steeper increase in BMI compared with children of Swedish mothers is important for further studies and for planning of preventive public health programs.     

Arbuscular mycorrhizal symbiosis regulates the physiological responses,ion distribution and relevant gene expression to trigger salt stress tolerance in pistachio

Mycorrhizal symbiosis is generally considered effective in ameliorating plant tolerance to abiotic stress by altering gene expression, and evaluation of genes involved in ion homeostasis and nutrient uptake. This study aimed to use arbuscular mycorrhizal fungus (AMF) to alleviate salinity stress and analyse relevant gene expression in pistachio plants under No/NaCl stress in greenhouse conditions. Arbuscular mycorrhizal symbiosis was used to study the physiological responses, ion distribution and relevant gene expression in pistachio plants under salinity stress. After four months of symbiosis, mycorrhizal root colonization showed a significant reduction in all tested parameters under salt stress treatment compared to non-saline treatment. Salinity affected the morphological traits, and decreased the nutrient content including N, P, Mg and Fe as well as K/Na and Ca/Na ratios, relative water content (RWC), membrane stability index (MSI), and increased the concentration of K, Ca and Na nutrient, glycine betaine, ROS and MDA. Inoculation of seedlings with AMF mitigated the negative effects of salinity on plant growth as indicated by increasing the root colonization, morphological traits, glycine betaine, RWC and MSI. Specifically, under salinity stress, shoot and root dry weight, P and Fe nutrient content, K/Na and Ca/Na ratio of AMF plants were increased by 53.2, 48.6, 71.6, 60.2, 87.5, and 80.1% respectively, in contrast to those of the NMF plants. The contents of Na, O^2•− and MDA in AMF plants were significantly decreased by 66.8, 36.8, and 23.1%, respectively at 250 mM NaCl. Moreover, salinity markedly increased SOS1, CCX2 and SKOR genes expression and the inoculation with AMF modulated these genes expression; however, NRT2.4, PHO1 and PIP2.4 gene expressions were increased by salinity and AMF. It could be concluded that inoculation of AMF with Rhizophagus irregularis conferred a larger endurance towards soil salinity in pistachio plants and stimulate the nutrient uptake and ionic homeostasis maintenance, superior RWC and osmoprotection, toxic ion partitioning, maintaining membrane integrity and the ion-relevant genes expression.