Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on ART.

R.Winzen and M.Kracht contributed equally to this workStabilization of mRNAs contributes to the strong and rapid induction of genes in the inflammatory response. The signaling mechanisms involved were investigated using a tetracycline-controlled expression system to determine the half-lives of interleukin (IL)-6 and IL-8 mRNAs. Transcript stability was low in untreated HeLa cells, but increased in cells expressing a constitutively active form of the MAP kinase kinase kinase MEKK1. Destabilization and signal-induced stabilization was transferred to the stable β-globin mRNA by a 161-nucleotide fragment of IL-8 mRNA which contains an AU-rich region, as well as by defined AU-rich elements (AREs) of the c-fos and GM-CSF mRNAs. Of the different MEKK1-activated signaling pathways, no significant effects on mRNA degradation were observed for the SAPK/JNK, extracellular regulated kinase and NF-κB pathways. Selective activation of the p38 MAP kinase (⍧SAPK2) pathway by MAP kinase kinase 6 induced mRNA stabilization. A dominant-negative mutant of p38 MAP kinase interfered with MEKK1 and also IL-1-induced stabilization. Furthermore, an active form of the p38 MAP kinase-activated protein kinase (MAPKAP K2 or MK2) induced mRNA stabilization, whereas a negative interfering MK2 mutant interfered with MAP kinase kinase 6-induced stabilization. These findings indicate that the p38 MAP kinase pathway contributes to cytokine/stress-induced gene expression by stabilizing mRNAs through an MK2-dependent, ARE-targeted mechanism.

Summary This systematic review examines the incidence of Immune Reconstitution Disease (IRD) in HIV-1 infected patients starting antiretroviral combination therapy (ART). We analysed 13103 patients from 54 cohort studies; 1685 patients developed IRD. Pooled incidences with 95% credibility intervals (CrI) were calculated using Bayesian methods. In patients with previously diagnosed AIDS-defining conditions the incidence was 37.7% (95% CrI 26.6–49.4%) for CMV retinitis, 19.5% (6.7–44.8%) for cryptococcal meningitis, 15.7% (9.7–24.5%) for tuberculosis, 16.7% (2.3–50.7%) for progressive multifocal leukencephalopathy and 6.4% (1.2–24.7%) for Kaposi’s sarcoma. The incidence of any type of IRD, based on studies of unselected patients starting ART, was 16.1% (11.1–22.9%). Lethality was 4.5% (2.1–8.6%) for any type of IRD, 3.2% (0.7–9.2%) for tuberculosis and 20.8% (5.0–52.7%) for cryptococcal meningitis. Meta-regression analyses showed that the incidence is largely determined by the CD4 cell count at the start of ART, with a high risk in patients starting below 50 cells/μl. Many of the IRD events might therefore be prevented with earlier initiation of ART.

The article summarizes our up to date knowledge about the morphology of the annelid, especially the polychaete, central and peripheral nervous system. Since the cephalic nervous system was in the focus of controversial discussions for decades, the structure of its neuropile, associated ganglia and nerves is reviewed in detail. The enormous variation of the ventral nerve cord and peripheral nerves is presented as well as a theory how this might have evolved. A ground pattern of the polychaete nervous system is suggested, based on developmental and regeneration studies.

The central complex is a topographically ordered neuropil structure in the center of the insect brain. It consists of three major subdivisions, the upper and lower divisions of the central body and the protocerebral bridge. To further characterize the role of this brain structure, we have recorded the responses of identified neurons of the central complex of the desert locust Schistocerca gregaria to visual stimuli. We report that particular types of central complex interneurons are sensitive to polarized light. Neurons showed tonic responses to linearly polarized light with spike discharge frequencies depending on e-vector orientation. For all neurons tested, e-vector response curves showed polarization opponency. Receptive fields of the recorded neurons were in the dorsal field of view with some neurons receiving input from both compound eyes and others, only from the ipsilateral eye. In addition to responses to polarized light, certain neurons showed tonic spike discharges to unpolarized light. Most polarization-sensitive neurons were associated with the lower division of the central body, but one type of neuron with arborizations in the upper division of the central body was also polarization-sensitive. Visual pathways signaling polarized light information to the central complex include projections via the anterior optic tubercle. Considering the receptive fields of the neurons and the biological significance of polarized light in insects, the central complex might serve a function in sky compass-mediated spatial navigation of the animals.

We have investigated the anatomical organization of the lower division of the central body in the brain of the locust Schistocerca gregaria. Bodian preparations, Golgi impregnations, and intracellular filling with Lucifer yellow have revealed that the lower division of the central body is organized into six horizontal layers and sixteen vertical columns. Neurons of the lower division of the central body have been classified into five types of tangential neuron (TL1-TL5) and two types of columnar neuron (CL1, CL2). TL1-TL4 neurons ramify in specific layers in the lower division of the central body and in the lateral triangle (TL1, TL2 neurons), the median olive (TL3 neurons), or the dorsal shell (TL4 neurons) of the lateral accessory lobe. TL5 neurons ramify in the protocerebral bridge, in the lateral accessory lobe, and in all layers of the lower division of the central body. The two types of columnar neurons have arborizations in the protocerebral bridge and in the lower division of the central body and project to the lateral triangle of the lateral accessory lobe (CL1 neurons) or to the lower subunit of the nodulus (CL2 neurons). Possible functional implications for the processing of neuronal information in the central complex are discussed.

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In Annelida, as well as in other invertebrate taxa, the nervous system is considered to be a very conservative organ system. Immunohistochemical investigations [use of anti-5-HT (serotonin), FMRFamide, and acetylated α-tubulin antibodies] in combination with laser scanning microscopy enable more detailed reanalyses of known structures and detection of new characteristics that are useful for phylogenetic analyses. One hypothesis enabled by such studies is outlined for the evolution of arrangements of the dorsal circumesophageal roots in polychaetes and oligochaetes. These roots are not a unique feature of polychaetes; they also occur in oligochaetes. According to the Articulata hypothesis of metazoan relationships, the specific structure of the rope-ladder-like nervous system is, among others, an autapomorphic characteristic that unifies Annelida and Arthropoda. Recent studies applying the techniques mentioned here, however, demonstrate that the annelidan bauchmark (central nervous system of the trunk), in contrast to the arthropod pattern, is highly variable in terms of the number and position of connectives and the number of commissures per segment. The variability of the neuronal architecture as well as a hypothesis on how it evolved will be introduced with the aid of regeneration and developmental studies. Furthermore, it is shown that hitherto unknown nerves are present in the peripheral nervous system.