Timing of ischemic insult alters fetal growth trajectory, maternal angiogenic balance, and markers of renal oxidative stress in the pregnant rat

Increased uterine artery resistance and angiogenic imbalance characterized by increased soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased free vascular endothelial growth factor (VEGF) are often associated with placental insufficiency and preeclampsia but not synonymous with hypertension. We hypothesized chronic reductions in utero-placental perfusion (RUPP) for 5 days (d) during either mid- (d12-d17) or late (d14-d19) gestation would have disparate effects on plasma sFlt-1 and VEGF levels and blood pressure. Five days of chronic RUPP was achieved by placement of silver clips on the abdominal aorta and ovarian arteries on either gestational d12 or d14. Arterial pressure was increased (P < 0.05) in RUPP vs. normal pregnant (NP) in both d17 (10%) and d19 (25%) groups, respectively. Circulating free VEGF was decreased (P < 0.05) and sFlt-1:VEGF ratio increased (P < 0.05) after 5 days of RUPP ending on d19 but not d17 compared with NP controls. Angiogenic imbalance, measured by an endothelial tube formation assay, was present in the d19 RUPP but not the d17 RUPP compared with age-matched NP rats. Five days of RUPP from days 14 to 19 decreased fetal and placental weights 10% (P < 0.01) compared with d19 NP controls. After 5 days of RUPP, from days 12 to 17 of pregnancy, fetal weights were 21% lighter (P < 0.01) compared with d17 NP controls, but placental weight was unchanged. These findings suggest that the timing during which placental insufficiency occurs may play an important role in determining the extent of alterations in angiogenic balance, fetal growth restriction, and the severity of placental ischemia-induced hypertension.     

In vivo baseline measurements of hip joint range of motion in suspensory and nonsuspensory anthropoids

Hominoids and atelines are known to use suspensory behaviors and are assumed to possess greater hip joint mobility than nonsuspensory monkeys, particularly for range of abduction. This assumption has greatly influenced how extant and fossil primate hip joint morphology has been interpreted, despite the fact that there are no data available on hip mobility in hominoids or Ateles. This study uses in vivo measurements to test the hypothesis that suspensory anthropoids have significantly greater ranges of hip joint mobility than nonsuspensory anthropoids. Passive hip joint mobility was measured on a large sample of anesthetized captive anthropoids (nonhuman hominids = 43, hylobatids = 6, cercopithecids = 43, Ateles = 6, and Cebus = 6). Angular and linear data were collected using goniometers and tape measures. Range of motion (ROM) data were analyzed for significant differences by locomotor group using ANOVA and phylogenetic regression. The data demonstrate that suspensory anthropoids are capable of significantly greater hip abduction and external rotation. Degree of flexion and internal rotation were not larger in the suspensory primates, indicating that suspension is not associated with a global increase in hip mobility. Future work should consider the role of external rotation in abduction ability, how the physical position of the distal limb segments are influenced by differences in ROM proximally, as well as focus on bony and soft tissue differences that enable or restrict abduction and external rotation at the anthropoid hip joint. Am J Phys Anthropol 153:417–434, 2014. © 2013 Wiley Periodicals, Inc.     

Multigene Phylogenetics Reveals Temporal Diversification of Major African Malaria Vectors

The major vectors of malaria in sub-Saharan Africa belong to subgenus Cellia. Yet, phylogenetic relationships and temporal diversification among African mosquito species have not been unambiguously determined. Knowledge about vector evolutionary history is crucial for correct interpretation of genetic changes identified through comparative genomics analyses. In this study, we estimated a molecular phylogeny using 49 gene sequences for the African malaria vectors An. gambiae, An. funestus, An. nili, the Asian malaria mosquito An. stephensi, and the outgroup species Culex quinquefasciatus and Aedes aegypti. To infer the phylogeny, we identified orthologous sequences uniformly distributed approximately every 5 Mb in the five chromosomal arms. The sequences were aligned and the phylogenetic trees were inferred using maximum likelihood and neighbor-joining methods. Bayesian molecular dating using a relaxed log normal model was used to infer divergence times. Trees from individual genes agreed with each other, placing An. nili as a basal clade that diversified from the studied malaria mosquito species 47.6 million years ago (mya). Other African malaria vectors originated more recently, and independently acquired traits related to vectorial capacity. The lineage leading to An. gambiae diverged 30.4 mya, while the African vector An. funestus and the Asian vector An. stephensi were the most closely related sister taxa that split 20.8 mya. These results were supported by consistently high bootstrap values in concatenated phylogenetic trees generated individually for each chromosomal arm. Genome-wide multigene phylogenetic analysis is a useful approach for discerning historic relationships among malaria vectors, providing a framework for the correct interpretation of genomic changes across species, and comprehending the evolutionary origins of this ubiquitous and deadly insect-borne disease.     

The Yeast Oxysterol Binding Protein Kes1 Maintains Sphingolipid Levels

The oxysterol binding protein family are amphitropic proteins that bind oxysterols, sterols, and possibly phosphoinositides, in a conserved binding pocket. The Saccharomyces cerevisiae oxysterol binding protein family member Kes1 (also known as Osh4) also binds phosphoinositides on a distinct surface of the protein from the conserved binding pocket. In this study, we determine that the oxysterol binding protein family member Kes1 is required to maintain the ratio of complex sphingolipids and levels of ceramide, sphingosine-phosphate and sphingosine. This inability to maintain normal sphingolipid homeostasis resulted in misdistribution of Pma1, a protein that requires normal sphingolipid synthesis to occur to partition into membrane rafts at the Golgi for its trafficking to the plasma membrane.     

REFOLDdb: a new and sustainable gateway to experimental protocols for protein refolding

Background

More than 7000 papers related to “protein refolding” have been published to date, with approximately 300 reports each year during the last decade. Whilst some of these papers provide experimental protocols for protein refolding, a survey in the structural life science communities showed a necessity for a comprehensive database for refolding techniques. We therefore have developed a new resource – “REFOLDdb” that collects refolding techniques into a single, searchable repository to help researchers develop refolding protocols for proteins of interest.

Results

We based our resource on the existing REFOLD database, which has not been updated since 2009. We redesigned the data format to be more concise, allowing consistent representations among data entries compared with the original REFOLD database. The remodeled data architecture enhances the search efficiency and improves the sustainability of the database. After an exhaustive literature search we added experimental refolding protocols from reports published 2009 to early 2017. In addition to this new data, we fully converted and integrated existing REFOLD data into our new resource. REFOLDdb contains 1877 entries as of March 17^th, 2017, and is freely available at http://p4d-info.nig.ac.jp/refolddb/.

Conclusion

REFOLDdb is a unique database for the life sciences research community, providing annotated information for designing new refolding protocols and customizing existing methodologies. We envisage that this resource will find wide utility across broad disciplines that rely on the production of pure, active, recombinant proteins. Furthermore, the database also provides a useful overview of the recent trends and statistics in refolding technology development.

     

Expression cloning of a cDNA encoding M1/69-J11d heat-stable antigens

The differentiation Ag identified by the mAb M1/69 and J11d (commonly referred to as heat-stable Ag) are found in structurally heterogeneous forms on the surfaces of many types of murine hemopoietic cells. The extinction of expression of these antigens is associated with thymocyte maturation and Ig class switching in B cells, as well as terminal differentiation of macrophages. A cDNA encoding the M1/69-J11d peptide was cloned from a hemopoietic progenitor cell line by immunoselection of COS cells transfected with expression libraries. The cloned cDNA is a copy of a gene that is transcribed in M1/69-J11d+ lymphoid, myeloid, and erythroid cells. This gene could be responsible for the expression of all forms of the M1/69-J11d Ag, although there are homologous genes that may encode some forms of the Ag that are specifically expressed in bone marrow. The cloned cDNA encodes a surprisingly small peptide, predicted to contain only 30 amino acids after removal of a signal sequence and displacement of the C-terminal region by the glycosyl-phosphatidylinositol group that anchors the peptide to the cell surface. Almost all of the mass of the M1/69-J11d Ag accumulates through extensive N- and O-linked glycosylation at multiple sites in the short peptide. These carbohydrates are likely to execute the functions of M1/69-J11d Ag, which could be specialized to each cell type as a consequence of differential glycosylation.     

MODBASE, a database of annotated comparative protein structure models

MODBASE (http://guitar.rockefeller.edu/modbase) is a relational database of annotated comparative protein structure models for all available protein sequences matched to at least one known protein structure. The models are calculated by MODPIPE, an automated modeling pipeline that relies on PSI-BLAST, IMPALA and MODELLER. MODBASE uses the MySQL relational database management system for flexible and efficient querying, and the MODVIEW Netscape plugin for viewing and manipulating multiple sequences and structures. It is updated regularly to reflect the growth of the protein sequence and structure databases, as well as improvements in the software for calculating the models. For ease of access, MODBASE is organized into different datasets. The largest dataset contains models for domains in 304 517 out of 539 171 unique protein sequences in the complete TrEMBL database (23 March 2001); only models based on significant alignments (PSI-BLAST E-value < 10^–4) and models assessed to have the correct fold are included. Other datasets include models for target selection and structure-based annotation by the New York Structural Genomics Research Consortium, models for prediction of genes in the Drosophila melanogaster genome, models for structure determination of several ribosomal particles and models calculated by the MODWEB comparative modeling web server.     

Toxicity of three acaricides to Tetranychus urticae (Tetranychidae: Acari) and Orius insidiosus (Anthocoridae: Hemiptera)

Management for twospotted spider mite, Tetranychus urticae Koch, populations in peanut, Arachis hypogaea L., relies on acaricides. The outcomes of acaricide applications are most predictable when complete information on their toxicity and specificity is available. Specifically, the degrees to which acaricides impact different stages of T. urticae and natural enemies combined determine the overall efficacy of an acaricide application. The objectives of this study were to determine stage-specific direct and residual efficacies of three acaricides (fenpropathrin, etoxazole, and propargite) against T. urticae, and the direct and residual toxicity of the acaricides to Orius insidiosus (Say) adults. Direct toxicity of acaricides to T. urticae was measured on peanut cuttings. All acaricide treatments caused significant mortality to a mixed stage population of T. urticae, and mortality did not differ among the acaricides 7 d after treatment. When toxicity to eggs was tested, the proportion of eggs that hatched for all acaricide treatments was significantly lower than the control, with etoxazole and propargite causing 100% mortality. Exposure to acaricide residues caused < 30% mortality of T. urticae adults 1 and 2 d after treatment and was not significantly different from the control. Fenpropathrin and propargite caused 100% mortality and etoxazole caused > 50% mortality of O. insidious adults after direct exposure to the acaricides. Residual toxicity of acaricides to O. insidiosus adults varied but remained toxic to O. insidiosus longer than to T. urticae. Fenpropathrin had the longest residual effect on O. insidiosus adults, causing > 95% mortality after 14 d; etoxazole and propargite caused < 30% mortality after 14 d.     

Scents and scents-ability: pollution disrupts chemical social recognition and shoaling in fish

Chemical cues are of enormous importance in mediating the behaviour of animals, enabling them to navigate throughout their habitats, to detect the presence of predators or prey and for social recognition-identifying and discriminating between conspecifics. In many species of freshwater fish, social recognition is known to be based primarily on chemical cues. Such recognition mechanisms are vulnerable to disruption by the presence of anthropogenic contaminants in the aquatic environment. Here we show that acute exposure to low, environmentally relevant dosages of the ubiquitous contaminant, 4-nonylphenol, can seriously affect social recognition and ultimately social organization in fishes. A 1 hour 0.5 microgl-1 dose was sufficient to alter the response of members of a shoaling fish species (juvenile banded killifish, Fundulus diaphanus) to conspecific chemical cues. Dosages of 1-2 microgl-1 caused killifish to orient away from dosed conspecifics, in both a flow channel and an arena. Given the overall importance of shoaling as an adaptive strategy against predators and for locating food, it is likely that its disruption by anthropogenic contaminants would have serious implications for fishes' fitness.     

Parasites ofSpodoptera exigua,S. eridania [Lep.: Noctuidae] andHerpetogramma bipunctalis [Lep.: Pyralidae] collected fromAmaranthus hybridus in field corn

Three species of lepidopterous larvae were collected fromAmaranthus hybridus L. growing in field corn during 1975 and 1976 at Hastings, Florida.Spodoptera exigua (Hubner) was the predominant species in May.Spodoptera eridania (Cramer) was predominant in June andHerpetogramma bipunctalis (F.) in July and August. Nine native species of parasites, representing theBraconidae, Eulophidae, Ichneumonidae andTachinidae, emerged from these larvae.Meteorus autographae Muesebeck emerged from bothS. exigua andS. eridania. TheTachinidae, Winthemia rufopicta (Bigot),Eucelatori rubentis (Coquillett) andLespensia sp., emerged from mixtures ofS. exigua andS. eridania. Apanteles marginiventris (Cresson),Temelucha sp., andChelonus texanus Cresson emerged from bothS. exigua andH. bipunctalis larvae, andEuplectrus platyhypenae Howard andOphion sp. emerged fromS. eridania. All the species of parasites from the lepidopterous larvae that feed onAmaranthus hybridus are also reported as parasites ofS. frugiperda, a serious pest of corn. Therefore these larvae onA. hybridus may be a source of the parasites found attackingS. frugiperda.