The entire N-terminal half of TatC is involved in twin-arginine precursor binding

Translocation of twin-arginine precursor proteins across the cytoplasmic membrane of Escherichia coli requires the three membrane proteins TatA, TatB, and TatC. TatC and TatB were shown to be involved in precursor binding. We have analyzed in vitro a number of single alanine substitutions in tatC that were previously shown to compromise in vivo the function of the Tat translocase. All tatC mutants that were defective in precursor translocation into cytoplasmic membrane vesicles concomitantly interfered with precursor binding not only to TatC but also to TatB. Hence structural changes of TatC that affect precursor targeting simultaneously abolish engagement of the twin-arginine signal sequence with TatB and block the formation of a functional Tat translocase. Since these phenotypes were observed for tatC mutations spread over the first half of TatC, this entire part of the molecule must globally be involved in precursor binding.     

Heparan sulfate proteoglycans regulate autophagy in Drosophila

Heparan sulfate-modified proteoglycans (HSPGs) are important regulators of signaling and molecular recognition at the cell surface and in the extracellular space. Disruption of HSPG core proteins, HS-synthesis, or HS-degradation can have profound effects on growth, patterning, and cell survival. The Drosophila neuromuscular junction provides a tractable model for understanding the activities of HSPGs at a synapse that displays developmental and activity-dependent plasticity. Muscle cell-specific knockdown of HS biosynthesis disrupted the organization of a specialized postsynaptic membrane, the subsynaptic reticulum (SSR), and affected the number and morphology of mitochondria. We provide evidence that these changes result from a dysregulation of macroautophagy (hereafter referred to as autophagy). Cellular and molecular markers of autophagy are all consistent with an increase in the levels of autophagy in the absence of normal HS-chain biosynthesis and modification. HS production is also required for normal levels of autophagy in the fat body, the central energy storage and nutritional sensing organ in Drosophila. Genetic mosaic analysis indicates that HS-dependent regulation of autophagy occurs non-cell autonomously, consistent with HSPGs influencing this cellular process via signaling in the extracellular space. These findings demonstrate that HS biosynthesis has important regulatory effects on autophagy and that autophagy is critical for normal assembly of postsynaptic membrane specializations.     

Mitotic checkpoint gene expression is tuned by codon usage bias

The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half‐lives and long protein half‐lives supports stable SAC protein levels. For the SAC genes mad2 ⁺ and mad3 ⁺, their short mRNA half‐lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1 ⁺ mRNA has a short half‐life despite a higher frequency of optimal codons, and despite the lack of known RNA‐destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co‐translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine‐tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.     

Feasibility of early infant diagnosis of HIV in resource-limited settings: the ANRS 12140-PEDIACAM study in Cameroon

Background

Early infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART, associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV according to national recommendations, in urban areas of Cameroon.

Methods/Findings

The ANRS12140-Pediacam study is a multisite cohort in which infants born to HIV-infected mothers were included before the 8^th day of life and followed. Collection of samples for HIV DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed by a second test on a different sample. Systematic HAART was offered to HIV-infected infants identified. The EID process was considered complete if infants were tested and HIV results provided to mothers/family before 7 months of age. During 2007–2009, 1587 mother-infant pairs were included in three referral hospitals; most infants (n = 1423, 89.7%) were tested for HIV, at a median age of 1.5 months (IQR, 1.4–1.6). Among them, 51 (3.6%) were HIV-infected. Overall, 1331 (83.9%) completed the process by returning for the result before 7 months (median age: 2.5 months (IQR, 2.4–3.0)). Incomplete process, that is test not performed, or result of test not provided or provided late to the family, was independently associated with late HIV diagnosis during pregnancy (adjusted odds ratio (aOR) = 1.8, 95%CI: 1.1 to 2.9, p = 0.01), absence of PMTCT prophylaxis (aOR = 2.4, 95%CI: 1.4 to 4.3, p = 0.002), and emergency caesarean section (aOR = 2.5, 95%CI: 1.5 to 4.3, p = 0.001).

Conclusions

In urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of non optimal diagnosis process should focus on women with late HIV diagnosis during pregnancy especially if they did not receive any PMTCT, or if complications occurred at delivery.     

Assessing the effect of complex ground types on ground‐dwelling arthropod movements with video monitoring: Dealing with concealed movements under a layer of plant residues

Understanding the effect of ground types on foraging movements of ground‐dwelling arthropods is a key step to managing their spatial distribution as required for successful conservation biological control. Indeed, fine movements at the centimeter scale can strongly influence the foraging ability of pest predators. However, because radio frequency identification or harmonic tracking techniques are not yet suitable for small species and video tracking focuses on uniform and light backgrounds, foraging movements have rarely been studied in relation to ground types. We present a method to track a ground‐dwelling arthropod (the earwig Euborellia caraibea) at night, walking on two contrasted ground types: bare soil and soil partly covered with a stratum of banana plant residues allowing individuals to hide periodically. The tracking of individuals within these ground types was achieved by infrared light, tagging individuals, video treatments, and semi‐automatic cleaning of trajectories. We tested different procedures to obtain segments with identical durations to quantify speeds and sinuosities. These procedures were characterized by the junction time gap between trajectory fragments, the rediscretization time of trajectories, and whether or not to use interpolation to fill in missing points in the trajectories. Earwigs exhibited significantly slower and more sinuous movements on soil with banana plant residues than on bare soil. Long time gaps for trajectory junction, extended rediscretization times, and interpolation were complementary means to integrate concealed movements in the trajectories. The highest slowdown in plant residues was detected when the procedure could account for longer periods under the residues. These results suggest that earwigs spent a significant amount of time concealed by the residues. Additionally, the residues strongly decreased the earwigs'' movement. Since the technical solutions presented in this study are inexpensive, easy to set up, and replicate, they represent valuable contributions to the emerging field of video monitoring.     

PALLIATIVE TREATMENT OF PROSTATISM

A study of 310 patients with prostatism who were not operated upon within a month following the first examination, was made in an effort to determine indications for operation in the patient with mild symptoms of prostatism. This study showed that long duration of symptoms, residual urine of more than 60 cc. and enlargement of the gland beyond Grade I are criteria for the necessity of operation. Palliative treatment is not always indicated. Patients with a soft, boggy prostate and those with more than a slight amount of infection in the prostate are benefited by light prostatic massage once weekly and stilbestrol given in doses of 1 mg. twice daily. Severe infection is treated by chemotherapy and bladder irrigations.