Targeted rescue of cancer-associated IDH1 mutant activity using an engineered synthetic antibody

We have utilized a high-diversity phage display library to engineer antibody fragments (Fabs) that can modulate the activity of the enzyme isocitrate dehydrogenase 1 (IDH1). We show that a conformation-specific Fab can reactivate an IDH1 mutant associated with brain tumors. The results show that this strategy is a first step towards developing "activator drugs" for a large number of genetic disorders where mutations have disrupted protein function

Characterization of bionanocellulose producing bacteria isolated from tapioca wastewater

This study was conducted to explore the potential of isolating bionanocellulose (BNC) producing bacteria from tapioca wastewater. A total of ten bacteria were successfully isolated and only one isolate named BPNC 3 produced white gelatinous materials in Hestrin and Schramm (HS) medium believed to be the BNC. According to 16S rRNA analysis, bacterium BPNC 3 was identified as Asaia sp. The BNC produced by Asaia sp. BPNC3 was characterized via Fourier transformed-infrared spectroscopy (FTIR) and Field-emission scanning electron microscope (FESEM). The FTIR spectrum showed the presence of two signature peaks at 3276.69 cm-1 and 2923.99 cm-1 indicative of nanocellulosic material. The FESEM micrograph showed characteristics of network fibrils typically present in nanocellulose structure

Engineering synthetic antibody binders for allosteric inhibition of prolactin receptor signaling

Background: Many receptors function by binding to multiple ligands, each eliciting a distinct biological output. The extracellular domain of the human prolactin receptor (hPRL-R) uses an identical epitope to bind to both prolactin (hPRL) and growth hormone (hGH), yet little is known about how each hormone binding event triggers the appropriate response. Findings: Here, we utilized a phage display library to generate synthetic antibodies (sABs) that preferentially modulate hPRL-R function in a hormone-dependent fashion. We determined the crystal structure of a sAB-hPRL-R complex, which revealed a novel allosteric mechanism of antagonism, whereby the sAB traps the receptor in a conformation more suitable for hGH binding than hPRL. This was validated by examining the effect of the sABs on hormone internalization via the hPRL-R and its downstream signaling pathway. Conclusions: The findings suggest that subtle structural changes in the extracellular domain of hPRL-R induced by each hormone determine the biological output triggered by hormone binding. We conclude that sABs generated by phage display selection can detect these subtle structural differences, and therefore can be used to dissect the structural basis of receptor-ligand specificity. Keywords: Prolactin signaling, Synthetic antibody, Phage display, Alloster

Merging cloned alloy models with colorful refactorings

Likewise to code, clone-and-own is a common way to create variants of a model, to explore the impact of different features while exploring the design of a software system. Previously, we have introduced Colorful Alloy, an extension of the popular Alloy language and toolkit to support feature-oriented design, where model elements can be annotated with feature expressions and further highlighted with different colors to ease understanding. In this paper we propose a catalog of refactorings for Colorful Alloy models, and show how they can be used to iteratively merge cloned Alloy models into a single feature-annotated colorful model, where the commonalities and differences between the different clones are easily perceived, and more efficient aggregated analyses can be performed.This work is financed by the ERDF — European Regional Development Fund through the Operational Programme for Competitiveness and Internationalisation – COMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT – Fundação para a Ciência e a Tecnologia within project PTDC/CCI-INF/29583/2017 – POCI-01-0145-FEDER-029583

Properties of fly ash concrete containing tropical soil bacteria

The autonomous crack healing process using microbiologically induced calcium carbonate precipitation (MICP) is a sustainable alternative to overcome propagation of micro-cracks and restore the durability of concrete. This paper presents the potential use of tropical soil bacteria as a self-healing agent for fly ash concrete. A solution of 107 cells/mL Lysinibacillus sphaericus (L. sphaericus), was selected to be the self-healing agent by replacing partially the amount of water. Concrete cube specimens with 30% fly ash, were cured under two conditions, which are water and air curing. The potential effects of the self-healing agent was evaluated in terms of the ultrasonic pulse velocity (UPV), initial surface absorption test (ISAT) and compressive strength. The initial results show an improvement of UPV and between 12% and 54% improvement on the compressive strength for the bacterial concrete compared to the control specimen. It was probably due to the presence of the microbial calcium carbonate that fills the concrete pores through the inclusion of bacteria in the concrete. However, based on the ISAT value, the direct addition of bacterial solution increased the concrete's permeability. Thus, further investigation is suggested to assess the self-healing effect towards permeability and compressive strength of bacterial concrete

Rectal cancer treatment and outcome in the elderly: an audit based on the Swedish rectal cancer registry 1995–2004

<p>Abstract</p> <p>Background</p> <p>Limited information is available regarding the effect of age on choice of surgical and oncological treatment for rectal cancer. The objective of this study was to assess the influence of age on treatment and outcome of rectal cancer.</p> <p>Methods</p> <p>We utilized data in the Swedish Rectal Cancer Registry (SRCR) from patients treated for rectal cancer in Sweden in 1995–2004.</p> <p>Results</p> <p>A total of 15,104 patients with rectal cancer were identified, 42.4% of whom were 75 years or older. Patients ≥75 years were less likely to have distant metastases than younger patients (14.8% vs. 17.8%, <it>P </it>< 0.001), and underwent abdominal tumor resection less frequently (68.5% vs. 84.4%, <it>P </it>< 0.001). Of 11,725 patients with abdominal tumor resection (anterior resection [AR], abdominoperineal excision [APE], and Hartmann's procedure [HA]), 37.4% were ≥75 years. Curative surgery was registered for 85.0% of patients ≥ 75 years and for 83.9% of patients < 75 years, <it>P </it>= 0.11. Choice of abdominal operation differed significantly between the two age groups for both curative and non-curative surgery, The frequency of APE was similar in both age groups (29.5% vs. 28.6%), but patients ≥75 years were more likely to have HA (16.9% vs. 4.9%) and less likely to have preoperative radiotherapy (34.3vs. 67.2%, <it>P </it>< 0.001). The relative survival rate at five years for all patients treated with curative intent was 73% (70–75%) for patients ≥75 years and 78% (77–79%) for patients < 75 years of age. Local recurrence rate was 9% (8–11%) for older and 8% (7–9%) for younger patients.</p> <p>Conclusion</p> <p>Treatment of rectal cancer is influenced by patient's age. Future studies should include younger and older patients alike to reveal whether or not age-related differences are purposive. Local recurrence following surgery for low tumors and quality of life aspects deserve particular attention.</p

Comprehensive ripeness-index for prediction of ripening level in mangoes by multivariate modelling of ripening behaviour

Prediction of ripeness level in climacteric fruits is essential for post-harvest handling. An index capable of predicting ripening level with minimum inputs would be highly beneficial to the handlers, processors and researchers in fruit industry. A study was conducted with Indian mango cultivars to develop a ripeness index and associated model. Changes in physicochemical, colour and textural properties were measured throughout the ripening period and the period was classified into five stages (unripe, early ripe, partially ripe, ripe and over ripe). Multivariate regression techniques like partial least square regression, principal component regression and multi linear regression were compared and evaluated for its prediction. Multi linear regression model with 12 parameters was found more suitable in ripening prediction. Scientific variable reduction method was adopted to simplify the developed model. Better prediction was achieved with either 2 or 3 variables (total soluble solids, colour and acidity). Cross validation was done to increase the robustness and it was found that proposed ripening index was more effective in prediction of ripening stages. Three-variable model would be suitable for commercial applications where reasonable accuracies are sufficient. However, 12-variable model can be used to obtain more precise results in research and development applications

Biodegradation of 4-aminobenzenesulfote by ralstonia sp.pba and hydrogenophaga sp. pbc isolated from textile treatment plant

A co-culture consisting of Hydrogenophaga sp. PBC and Ralstonia sp. PBA, isolated from textile wastewater treatment plant could tolerate up to 100 mM 4-aminobenzenesulfonate (4-ABS) and utilize it as sole carbon, nitrogen and sulfur source under aerobic condition. The biodegradation of 4-ABS resulted in the release of nitrogen and sulfur in the form of ammonium and sulfate respectively. Ninety-eight percent removal of chemical oxygen demand attributed to 20 mM of 4-ABS in cell-free supernatant could be achieved after 118 h. Effective biodegradation of 4-ABS occurred at pH ranging from 6 to 8. During batch culture with 4-ABS as sole carbon and nitrogen source, the ratio of strain PBA to PBC was dynamic and a critical concentration of strain PBA has to be reached in order to enable effective biodegradation of 4-ABS. Haldane inhibition model was used to fit the degradation rate at different initial concentrations and the parameters µ(max), K(s) and K(i) were determined to be 0.13 h?¹, 1.3 mM and 42 mM respectively. HPLC analyses revealed traced accumulation of 4-sulfocatechol and at least four unidentified metabolites during biodegradation. This is the first study to report on the characterization of 4-ABS-degrading bacterial consortium that was isolated from textile wastewater treatment plant