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.     

Organism-Scale Modeling of Early Drosophila Patterning via Bone Morphogenetic Proteins

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Highlights? Capturing 3D spatiotemporal content of expression data increases model utility ? Embryo geometry shapes signaling; prepatterns compensate in misshapen embryos ? Cell-surface binding proteins compensate for weak ligand/inhibitor/receptor binding ? BMP-mediated patterning is “nearly” scale-invariant     

The qualitative dynamics of a class of biochemical control circuits

Summary The dynamical behavior of a class of biochemical control circuits that regulate enzyme or protein synthesis by end-product feedback is analyzed. Both inducible and repressible systems are studied and it is proven that in the former unique steady states are globally asymptotically stable. This precludes periodic solutions in these systems. A similar result holds for repressible systems under certain constraints on kinetic parameters and binding contants. However, when the reaction sequence is sufficiently long, or when a large enough number of effector molecules bind to each represser molecule, repressible systems can show zero-amplitude (soft) bifurcations: these are predicted by Hopf's bifurcation theorem.     

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.     

A chemotactic model for the advance and retreat of the primitive streak in avian development

The formation of the primitive streak in early avian development marks the onset of gastrulation, during which large scale cell movement leads to a trilaminar blastoderm comprising prospective endodermal, mesodermal and ectodermal tissue. During streak formation a specialized group of cells first moves anteriorly as a coherent column, beginning from the posterior end of the prospective anterior-posterior axis (a process called progression), and then reverses course and returns to the most posterior point on the axis (a process called regression). To date little is known concerning the mechanisms controlling either progression or regression. Here we develop a model in which chemotaxis directs the cell movement and which is capable of reproducing the principal features connected with progression and regression of the primitive streak. We show that this model exhibits a number of experimentally-observed features of normal and abnormal streak development, and we propose a number of experimental tests which may serve to illuminate the mechanisms. This paper represents the first attempt to model the global features of primitive streak formation, and provides an initial stage in the development of a more biologically-realistic discrete cell model that will allow for variation of properties between cells and control over movement of individual cells.     

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.     

Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo

Patterning the dorsal surface of the Drosophila blastoderm embryo requires Decapentaplegic (Dpp) and Screw (Scw), two BMP family members. Signaling by these ligands is regulated at the extracellular level by the BMP binding proteins Sog and Tsg. We demonstrate that Tsg and Sog play essential roles in transporting Dpp to the dorsal-most cells. Furthermore, we provide biochemical and genetic evidence that a heterodimer of Dpp and Scw, but not the Dpp homodimer, is the primary transported ligand and that the heterodimer signals synergistically through the two type I BMP receptors Tkv and Sax. We propose that the use of broadly distributed Dpp homodimers and spatially restricted Dpp/Scw heterodimers produces the biphasic signal that is responsible for specifying the two dorsal tissue types. Finally, we demonstrate mathematically that heterodimer levels can be less sensitive to changes in gene dosage than homodimers, thereby providing further selective advantage for using heterodimers as morphogens.     

粘虫(Pseudaletia separata(Walker))生殖系统的解剖

本文内容是研究粘虫(Pseudaletia separata(Walker)生殖系统的形态构造。全文分为雄性内部生殖器、雄性外部生殖器、雌性内部生殖器及雌性外部生殖器四部分。 粘虫的雄性内生殖器中, 有睾丸一对, 左右并列, 呈扁椭圆形, 外被紫红色睾丸膜; 输精管一对, 基部膨大成二对贮精囊; 射精管分成复射精管及单射精管两部分。雄性外生殖器的构造极为复杂, 第9腹节的背、腹板分别形成马鞍状的背兜及基腹弧; 第10腹节仅有其附肢特化成钩形突、颚形突和背兜侧突等; 抱握器占雄性外生殖器中的大部分, 其顶上角具长约1毫米的端刺一枚, 此为本种特征之一, 可以此与近似种区别; 阳茎由基部球状的阳茎囊和端部柄状的阳茎端组成, 内具内阳茎及角状器:雄性外生殖器中有关器官的肌肉来源亦作了叙述。 精液是以贮存于精球的方式授入雌体, 精球分为精球体、精球柄及系带三部分。 雌性内生殖器中, 卵巢为多滋式, 一对, 各由四个卵巢管组成, 两组卵巢管再与一对侧输卵管相连, 后者通入中输卵管中, 中输卵管后端连有外生殖腔, 其外方的开口是为产卵孔; 受精囊为长形梨状物, 分成主囊及副囊两部分, 两者在顶部愈合, 并由此发出受精管与外生殖腔相通, 在主囊顶端有受精囊腺; 附腺一对, 与附腺囊相连, 后者通入附腺主囊, 并由此开口入外生殖腔。雌性外生殖器是由交配囊和产卵器组成, 前者复可分成囊导管、囊体及囊颈三部分, 其外方的开口为交配囊孔, 有导精管从囊颈连于外生殖腔; 产卵器由第8、9腹节组成, 非呈特殊构造。