Alternate processing of Flt1 transcripts is directed by conserved cis-elements within an intronic region of FLT1 that reciprocally regulates splicing and polyadenylation

The vascular endothelial growth factor receptor, Flt1 is a transmembrane receptor co-expressed with an alternate transcript encoding a secreted form, sFlt1, that functions as a competitive inhibitor of Flt1. Despite shared transcription start sites and upstream regulatory elements, sFlt1 is in far greater excess of Flt1 in the human placenta. Phorbol myristic acid and dimethyloxalylglycine differentially stimulate sFlt1 compared to Flt1 expression in vascular endothelial cells and in cytotrophoblasts. An FLT1 minigene construct containing exon 13, 14 and the intervening region, recapitulates mRNA processing when transfected into COS-7, with chimeric intronic sFlt1 transcripts arising by intronic polyadenylation and other Flt1/sFlt1 transcripts by alternate splicing. Inclusion of exon 15 but not 14 had a modest stimulatory effect on the abundance of sFlt1. The intronic region containing the distal poly(A) signal sequences, when transferred to a heterologous minigene construct, inhibited splicing but only when cloned in sense orientation, consistent with the presence of a directional cis-element. Serial deletional and targeted mutational analysis of cis-elements within intron 13 identified intronic poly(A) signal sequences and adjacent cis-elements as the principal determinants of the relative ratio of intronic sFlt1 and spliced Flt1. We conclude that intronic signals reciprocally regulate splicing and polyadenylation and control sFlt1 expression

Evaluation of the profile of alopecia areata and the prevalence of thyroid function test abnormalities and serum autoantibodies in Iranian patients

BACKGROUND: The study aimed at evaluating the prevalence of thyroid function abnormalities in patients with alopecia areata (AA) and its association with other autoimmune diseases and various autoimmune antibodies. METHOD: We retrospectively analyzed medical records of 123 patients with AA. The main site of involvement, pattern, and extent of alopecia as well as presence of the similar disease in first-degree family members and serologic status of patients were recorded. RESULTS: Participating in the study were 57 males and 66 females (6 to 59 years old). In the majority of patients (69.9%) the disease was manifested in the first two decades of life. Patients with family members having alopecia were recorded in 24.4%. Thyroid function abnormalities were found in 8.9% of patients. Positive autoimmune antibodies were associated with AA in 51.4% of patients with no significant association between the severity and duration of disease and presence of these antibodies. CONCLUSION: The incidence of positive auto-immune antibodies in Iranian patients is higher than previous reports. Concerning the female:male ratio, thyroid function tests and the prevalence of alopecia in first-degree relatives, our results are compatible with previous data obtained from different ethnic populations. Previous reports documented that a greater severity and longer duration of AA were seen in the early onset forms; however our result are relatively different which could be explained by differences in genetic factors

Closed-Loop Recycling of Copper from Waste Printed Circuit Boards Using Bioleaching and Electrowinning Processes

International audienceIn the present study, a model of closed-loop recycling of copper from PCBs is demonstrated, which involves the sequential application of bioleaching and electrowinning to selectively extract copper. This approach is proposed as part of the solution to resolve the challenging ever-increasing accumulation of electronic waste, e-waste, in the environment. This work is targeting copper, the most abundant metal in e-waste that represents up to 20% by weight of printed circuit boards (PCBs). In the first stage, bioleaching was tested for different pulp densities (0.25–1.00% w/v) and successfully used to extract multiple metals from PCBs using the acidophilic bacterium, Acidithiobacillus ferrooxidans. In the second stage, the method focused on the recovery of copper from the bioleachate by electrowinning. Metallic copper foils were formed, and the results demonstrated that 75.8% of copper available in PCBs had been recovered as a high quality copper foil, with 99 + % purity, as determined by energy dispersive X-ray analysis and Inductively-Coupled Plasma Optical Emission Spectrometry. This model of copper extraction, combining bioleaching and electrowinning, demonstrates a closed-loop method of recycling that illustrates the application of bioleaching in the circular economy. The copper foils have the potential to be reused, to form new, high value copper clad laminate for the production of complex printed circuit boards for the electronics manufacturing industry. Graphic Abstract: [Figure not available: see fulltext.] © 2020, The Author(s)

Enhancing Perceived Safety in Human–Robot Collaborative Construction Using Immersive Virtual Environments

Advances in robotics now permit humans to work collaboratively with robots. However, humans often feel unsafe working alongside robots. Our knowledge of how to help humans overcome this issue is limited by two challenges. One, it is difficult, expensive and time-consuming to prototype robots and set up various work situations needed to conduct studies in this area. Two, we lack strong theoretical models to predict and explain perceived safety and its influence on human–robot work collaboration (HRWC). To address these issues, we introduce the Robot Acceptance Safety Model (RASM) and employ immersive virtual environments (IVEs) to examine perceived safety of working on tasks alongside a robot. Results from a between-subjects experiment done in an IVE show that separation of work areas between robots and humans increases perceived safety by promoting team identification and trust in the robot. In addition, the more participants felt it was safe to work with the robot, the more willing they were to work alongside the robot in the future.University of Michigan Mcubed Grant: Virtual Prototyping of Human-Robot Collaboration in Unstructured Construction EnvironmentsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145620/1/You et al. forthcoming in AutCon.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145620/4/You et al. 2018.pdfDescription of You et al. 2018.pdf : Published Versio

Lessons learned in a decade of research software engineering gpu applications

After years of using Graphics Processing Units (GPUs) to accelerate scientific applications in fields as varied as tomography, computer vision, climate modeling, digital forensics, geospatial databases, particle physics, radio astronomy, and localization microscopy, we noticed a number of technical, socio-technical, and non-technical challenges that Research Software Engineers (RSEs) may run into. While some of these challenges, such as managing different programming languages within a project, or having to deal with different memory spaces, are common to all software projects involving GPUs, others are more typical of scientific software projects. Among these challenges we include changing resolutions or scales, maintaining an application over time and making it sustainable, and evaluating both the obtained results and the achieved performance

Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice

<div><p>Objective</p><p>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.</p><p>Methods</p><p>Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.</p><p>Results</p><p>Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10^-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10^-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).</p><p>Conclusions</p><p>A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the <i>in vivo</i> pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</p></div