Comparative study of the extracellular proteome of Sulfolobus species reveals limited secretion

Although a large number of potentially secreted proteins can be predicted on the basis of genomic distribution of signal sequence-bearing proteins, protein secretion in Archaea has barely been studied. A proteomic inventory and comparison of the growth medium proteins in three hyperthermoacidophiles, i.e., Sulfolobus solfataricus, S. acidocaldarius and S. tokodaii, indicates that only few proteins are freely secreted into the growth medium and that the majority originates from cell envelope bound forms. In S. acidocaldarius both cell-associated and secreted α-amylase activities are detected. Inactivation of the amyA gene resulted in a complete loss of activity, suggesting that the same protein is responsible for the a-amylase activity at both locations. It is concluded that protein secretion in Sulfolobus is a limited process, and it is suggested that the S-layer may act as a barrier for the free diffusion of folded proteins into the medium

The precision of axon targeting of mouse olfactory sensory neurons requires the BACE1 protease

The β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is necessary to generate the Aβ peptide, which is implicated in Alzheimer's disease pathology. Studies show that the expression of BACE1 and its protease activity are tightly regulated, but the physiological function of BACE1 remains poorly understood. Recently, numerous axon guidance proteins were identified as potential substrates of BACE1. Here, we examined the consequences of loss of BACE1 function in a well-defined in vivo model system of axon guidance, mouse olfactory sensory neurons (OSNs). The BACE1 protein resides predominantly in proximal segment and the termini of OSN axons, and the expression of BACE1 inversely correlates with odor-evoked neural activity. The precision of targeting of OSN axons is disturbed in both BACE1 null and, surprisingly, in BACE1 heterozygous mice. We propose that BACE1 cleavage of axon guidance proteins is essential to maintain the connectivity of OSNs in vivo

Maternal position during the first stage of labor: a systematic review

BACKGROUND: Policy makers and health professionals are progressively using evidence-based rationale to guide their decisions. There has long been controversy regarding which maternal position is more appropriate during the first stage of labor. This problem has been examined often and repeatedly and the optimal recommendation remains unclear. METHODS: This is a systematic review of the effect of maternal position during the first stage of labor. The main question addressed here is: Does encouraging women to adopt an upright position or to ambulate during the first stage of labor reduce the duration of this stage? All randomized controlled trials carried out to assess this effect were taken into consideration in this review. The following electronic databases were accessed to identify studies: MEDLINE, Popline, the Scientific Electronic Library On-line and the Latin American and Caribbean Health Science Information. Citation eligibility was independently assessed by two reviewers. The methodological quality of each trial was also evaluated independently by two reviewers and a trial under consideration was included only when consensus had been attained. Allocation concealment and screening for the occurrence of attrition, performance and detection biases were considered when studies were appraised. The decision whether to perform data pooling was based on the clinical similarity of studies. RESULTS: The search strategy resulted in 260 citations, of which 18 were assessed in full-text. Nine eligible randomized controlled trials were included in the systematic review. Randomization methods were not fully described in eight studies. The allocation concealment was considered adequate in four studies and unclear in five. The investigators pooled the data from seven studies in which the length of the first stage of labor and results were in favor of the intervention, but the high level of heterogeneity (I(2 )= 88.4%) impaired the meaning of this finding. The intervention did not affect other outcomes studied (mode of delivery, use of analgesia, labor augmentation and condition of the child at birth). CONCLUSION: Adoption of the upright position or ambulation during first stage of labor may be safe, but considering the available evidence and its consistency, it cannot be recommended as an effective intervention to reduce duration of the first stage of labor

A randomised controlled trial for the effectiveness of intra-articular Ropivacaine and Bupivacaine on pain after knee arthroscopy: the DUPRA (DUtch Pain Relief after Arthroscopy)-trial

In this double-blinded, randomised clinical trial, the aim was to compare the analgesic effects of low doses of intra-articular Bupivacaine and Ropivacaine against placebo after knee arthroscopy performed under general anaesthesia. A total of 282 patients were randomised to 10 cc NaCl 0.9%, 10 cc Bupivacaine 0.5% or 10 cc Ropivacaine 0.75%. Patients received the assigned therapy by intra-articular injection after closure of the portal. Pain and satisfaction were measured at one, 4 h and 5-7 days after arthroscopy with Numerical Rating Scale (NRS) -scores. NSAID consumption was also recorded. One-h NRS-scores at rest were higher in the NaCl group compared with the Bupivacaine group (P <0.01), 1 h NRS-scores in flexion were higher in the NaCl group compared with the Bupivacaine (P <0.01) and Ropivacaine (P <0.01) groups. NRS-satisfaction at 4 h was higher for the Bupivacaine group compared with the NaCl group (P = 0.01). Differences in NRS-scores were significant but low in magnitude. NSAID consumption was lower in the Bupivacaine group compared with the NaCl group (P <0.01). The results of this randomised clinical trial demonstrate improved analgesia after administration of low doses of intra-articular Bupivacaine and Ropivacaine after arthroscopy of the knee. Considering reports of Bupivacaine and Ropivacaine being chondrotoxic agents and the relatively small improvement on patient comfort found in this trial, it is advised to use systemic anaesthetic instead of intra-articular Bupivacaine or Ropivacaine for pain relief after knee arthroscopy.

The Cluster Variation Method for Efficient Linkage Analysis on Extended Pedigrees

BACKGROUND: Computing exact multipoint LOD scores for extended pedigrees rapidly becomes infeasible as the number of markers and untyped individuals increase. When markers are excluded from the computation, significant power may be lost. Therefore accurate approximate methods which take into account all markers are desirable. METHODS: We present a novel method for efficient estimation of LOD scores on extended pedigrees. Our approach is based on the Cluster Variation Method, which deterministically estimates likelihoods by performing exact computations on tractable subsets of variables (clusters) of a Bayesian network. First a distribution over inheritances on the marker loci is approximated with the Cluster Variation Method. Then this distribution is used to estimate the LOD score for each location of the trait locus. RESULTS: First we demonstrate that significant power may be lost if markers are ignored in the multi-point analysis. On a set of pedigrees where exact computation is possible we compare the estimates of the LOD scores obtained with our method to the exact LOD scores. Secondly, we compare our method to a state of the art MCMC sampler. When both methods are given equal computation time, our method is more efficient. Finally, we show that CVM scales to large problem instances. CONCLUSION: We conclude that the Cluster Variation Method is as accurate as MCMC and generally is more efficient. Our method is a promising alternative to approaches based on MCMC sampling

Reduced Myelin Basic Protein and Actin-Related Gene Expression in Visual Cortex in Schizophrenia

Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls. We first carried out a preliminary array screen of pooled RNA, and then used RT-PCR to quantify five mRNAs which the array identified as differentially expressed in schizophrenia (myelin basic protein [MBP], myelin-oligodendrocyte glycoprotein [MOG], β-actin [ACTB], thymosin β-10 [TB10], and superior cervical ganglion-10 [SCG10]). Reduced mRNA levels were confirmed by RT-PCR for MBP, ACTB and TB10. The MBP reduction was limited to transcripts containing exon 2. ACTB and TB10 mRNAs were also decreased in bipolar disorder. None of the transcripts were altered in subjects with major depression. Reduced MBP mRNA in schizophrenia replicates findings in other brain regions and is consistent with oligodendrocyte involvement in the disorder. The decreases in expression of ACTB, and the actin-binding protein gene TB10, suggest changes in cytoskeletal organisation. The findings confirm that the primary visual cortex shows molecular alterations in schizophrenia and extend the evidence for a widespread, rather than focal, cortical pathophysiology

O2-Filled Swimbladder Employs Monocarboxylate Transporters for the Generation of O2 by Lactate-Induced Root Effect Hemoglobin

The swimbladder volume is regulated by O2 transfer between the luminal space and the blood In the swimbladder, lactic acid generation by anaerobic glycolysis in the gas gland epithelial cells and its recycling through the rete mirabile bundles of countercurrent capillaries are essential for local blood acidification and oxygen liberation from hemoglobin by the “Root effect.” While O2 generation is critical for fish flotation, the molecular mechanism of the secretion and recycling of lactic acid in this critical process is not clear. To clarify molecules that are involved in the blood acidification and visualize the route of lactic acid movement, we analyzed the expression of 17 members of the H+/monocarboxylate transporter (MCT) family in the fugu genome and found that only MCT1b and MCT4b are highly expressed in the fugu swimbladder. Electrophysiological analyses demonstrated that MCT1b is a high-affinity lactate transporter whereas MCT4b is a low-affinity/high-conductance lactate transporter. Immunohistochemistry demonstrated that (i) MCT4b expresses in gas gland cells together with the glycolytic enzyme GAPDH at high level and mediate lactic acid secretion by gas gland cells, and (ii) MCT1b expresses in arterial, but not venous, capillary endothelial cells in rete mirabile and mediates recycling of lactic acid in the rete mirabile by solute-specific transcellular transport. These results clarified the mechanism of the blood acidification in the swimbladder by spatially organized two lactic acid transporters MCT4b and MCT1b

A Global Fireball Observatory

The world's meteorite collections contain a very rich picture of what the early Solar System would have been made of, however the lack of spatial context with respect to their parent population for these samples is an issue. The asteroid population is equally as rich in surface mineralogies, and mapping these two populations (meteorites and asteroids) together is a major challenge for planetary science. Directly probing asteroids achieves this at a high cost. Observing meteorite falls and calculating their pre-atmospheric orbit on the other hand, is a cheaper way to approach the problem. The Global Fireball Observatory (GFO) collaboration was established in 2017 and brings together multiple institutions (from Australia, USA, Canada, Morocco, Saudi Arabia, the UK, and Argentina) to maximise the area for fireball observation time and therefore meteorite recoveries. The members have a choice to operate independently, but they can also choose to work in a fully collaborative manner with other GFO partners. This efficient approach leverages the experience gained from the Desert Fireball Network (DFN) pathfinder project in Australia. The state-of-the art technology (DFN camera systems and data reduction) and experience of the support teams is shared between all partners, freeing up time for science investigations and meteorite searching. With all networks combined together, the GFO collaboration already covers 0.6% of the Earth's surface for meteorite recovery as of mid-2019, and aims to reach 2% in the early 2020s. We estimate that after 5 years of operation, the GFO will have observed a fireball from virtually every meteorite type. This combined effort will bring new, fresh, extra-terrestrial material to the labs, yielding new insights about the formation of the Solar System.Comment: Accepted in PSS. 19 pages, 9 figure