Inference of Biochemical S-Systems via Mixed-Variable Multiobjective Evolutionary Optimization

Inference of the biochemical systems (BSs) via experimental data is important for understanding how biochemical components in vivo interact with each other. However, it is not a trivial task because BSs usually function with complex and nonlinear dynamics. As a popular ordinary equation (ODE) model, the S-System describes the dynamical properties of BSs by incorporating the power rule of biochemical reactions but behaves as a challenge because it has a lot of parameters to be confirmed. This work is dedicated to proposing a general method for inference of S-Systems by experimental data, using a biobjective optimization (BOO) model and a specially mixed-variable multiobjective evolutionary algorithm (mv-MOEA). Regarding that BSs are sparse in common sense, we introduce binary variables indicating network connections to eliminate the difficulty of threshold presetting and take data fitting error and the L0-norm as two objectives to be minimized in the BOO model. Then, a selection procedure that automatically runs tradeoff between two objectives is employed to choose final inference results from the obtained nondominated solutions of the mv-MOEA. Inference results of the investigated networks demonstrate that our method can identify their dynamical properties well, although the automatic selection procedure sometimes ignores some weak connections in BSs

Inference of Biochemical S-Systems via Mixed-Variable Multiobjective Evolutionary Optimization

Inference of the biochemical systems (BSs) via experimental data is important for understanding how biochemical components in vivo interact with each other. However, it is not a trivial task because BSs usually function with complex and nonlinear dynamics. As a popular ordinary equation (ODE) model, the S-System describes the dynamical properties of BSs by incorporating the power rule of biochemical reactions but behaves as a challenge because it has a lot of parameters to be confirmed. This work is dedicated to proposing a general method for inference of S-Systems by experimental data, using a biobjective optimization (BOO) model and a specially mixed-variable multiobjective evolutionary algorithm (mv-MOEA). Regarding that BSs are sparse in common sense, we introduce binary variables indicating network connections to eliminate the difficulty of threshold presetting and take data fitting error and the 0 -norm as two objectives to be minimized in the BOO model. Then, a selection procedure that automatically runs tradeoff between two objectives is employed to choose final inference results from the obtained nondominated solutions of the mv-MOEA. Inference results of the investigated networks demonstrate that our method can identify their dynamical properties well, although the automatic selection procedure sometimes ignores some weak connections in BSs

Kwas zoledronowy stosowany przez dwa lata u Chinek z osteoporozą pomenopauzalną zwiększa gęstość mineralną tkanki kostnej i poprawia jakość życia związaną ze stanem zdrowia

Introduction: Osteoporosis is characterised by decreased bone mass and weakened bones, with an increased risk of fractures. Osteoporotic fracture, the most serious complication of osteoporosis, is related not only to lower bone mineral density (BMD), but also falls. Osteoporosis and fractures are associated with a decreased health-related quality of life (HRQL). Zoledronic acid (ZOL) is an intravenous once-yearly bisphosphonate that has been shown to be effective and safe in improving BMD and reducing fracture risk in controlled clinical trials.Material and methods: In this self-controlled, prospective trial, 220 postmenopausal women with osteoporosis (mean age 67 years) received a single infusion of ZOL 5 mg at baseline and month 12. BMD, HRQL and Fall Index (FI) were measured at baseline, and months 12 and 24 (before each use of ZOL). The main outcome measures were the changes in lumbar spine and hip BMD and the changes in HRQL, the Short Form-36 questionnaire (SF-36). Additional comparisons were based on the FI. LSD multiple comparisons were used in the comparisons of BMD, SF-36 domain scores and FI.Results: The patients had significantly higher L1-4, total hip, femoral neck and trochanter BMD (P < 0.05) with improved HRQL (P < 0.05) over two years of treatment of once-yearly ZOL 5mg. FI was reduced (P < 0.05) with oral daily elemental calcium and vitamin D in the treatment course.Conclusions: ZOL improves BMD and HRQL, especially in the physical aspects, over two years of treatment in women with postmenopausal osteoporosis, and can help improve balance ability. (Endokrynol Pol 2014; 65 (2): 96–104)Wstęp: Osteoporoza to schorzenie cechujące się obniżeniem masy kostnej i wytrzymałości mechanicznej kości z towarzyszącym zwiększeniem ryzyka złamań. Złamania osteoporotyczne, będące najpoważniejszym powikłaniem osteoporozy, wiążą się nie tylko z obniżoną gęstością mineralną tkanki kostnej (BMD, bone mineral density) ale też z upadkami. Z osteoporozą i złamaniami wiąże się obniżenie jakości życia związanej ze stanem zdrowia (HRQoL, health-related quality of life). Kwas zoledronowy (ZOL) to bisfosfonian w postaci dożylnej przeznaczony do podawania raz w roku, w przypadku którego w badaniach klinicznych z grupą kontrolną wykazano skuteczność i bezpieczeństwo w zwiększaniu BMD i zmniejszaniu ryzyka złamań.Materiał i metody: Autorzy przeprowadzili samodzielnie kontrolowane, prospektywne badanie z udziałem 220 znajdujących się w wieku pomenopauzalnym kobiet z osteoporozą (średnia wieku 67 lat), które otrzymały jednorazowo roztwór ZOL w dawce 5 mg na początku badania i 12 miesięcy później. Na początku badania, w 12. miesiącu i w 24. miesiącu badania (za każdym razem przed podaniem ZOL) oznaczano BMD, HRQoL i wskaźnik upadków (FI, fall index). Główne punkty końcowe obejmowały zmiany BMD w odcinku lędźwiowym kręgosłupa i BMD w okolicy biodra, a także zmiany HRQoL w kwestionariuszu SF-36. Dodatkowe porównania będą oparte na FI. W porównaniach wartości BMD, liczby punktów w poszczególnych domenach kwestionariusza SF-36 i wartości FI zastosowano metodę wielokrotnych porównań najmniejszej istotnej różnicy.Wyniki: U pacjentek stwierdzono znamiennie większe wartości BMD na poziomie L1–4, BMD w całkowitym obszarze biodra, BMD w obrębie szyjki kości udowej oraz BMD w obrębie krętarza (p < 0,05) oraz znamienną poprawę HRQoL (p < 0,05) w okresie 2 lat leczenia podawanym raz w roku ZOL w dawce 5 mg. Stwierdzono też zmniejszenie FI (p < 0,05) dzięki codziennemu przyjmowaniu wapnia i witaminy D w okresie leczenia.Wnioski: Stosowanie ZOL prowadzi do poprawy BMD i HRQoL, zwłaszcza w aspekcie fizycznym, w okresie 2 lat stosowania u kobiet z osteoporozą pomenopauzalną, i może przyczyniać się do poprawy zdolności utrzymania równowagi. (Endokrynol Pol 2014; 65 (2): 96–104

GDF15 Regulates Malat-1 Circular RNA and Inactivates NFκB Signaling Leading to Immune Tolerogenic DCs for Preventing Alloimmune Rejection in Heart Transplantation

Recombinant human growth differentiation factor 15 (rhGDF15) affects dendritic cell (DC) maturation. However, whether GDF15 is expressed in DCs and its roles and signaling in DCs remain largely unknown. It is unclear whether GDF15-DCs can induce immune tolerance in heart transplantation (HT). This study aims to understand the impact of endogenous GDF15 on DC's development, function, underlying molecular mechanism including circular RNA (circRNA). This study will also explore GDF15-DC-mediated immune modulation in HT. Bone marrow (BM) derived DCs were cultured and treated to up- or down regulate GDF15 expression. Phenotype and function of DCs were detected. Expression of genes and circRNAs was determined by qRT-PCR. The signaling pathways activated by GDF15 were examined. The impact of GDF15 treated DCs on preventing allograft immune rejection was assessed in a MHC full mismatch mouse HT model. Our results showed that GDF15 was expressed in DCs. Knockout of GDF15 promoted DC maturation, enhanced immune responsive functions, up-regulated malat-1 circular RNA (circ_Malat 1), and activated the nuclear factor kappa B (NFκB) pathway. Overexpression of GDF15 in DCs increased immunosuppressive/inhibitory molecules, enhanced DCs to induce T cell exhaustion, and promoted Treg generation through IDO signaling. GDF15 utilized transforming growth factor (TGF) β receptors I and II, not GFAL. Administration of GDF15 treated DCs prevented allograft rejection and induced immune tolerance in transplantation. In conclusion, GDF15 induces tolerogenic DCs (Tol-DCs) through inhibition of circ_Malat-1 and the NFκB signaling pathway and up-regulation of IDO. GDF15-DCs can prevent alloimmune rejection in HT

Colour removal and its mechanisms in textile wastewater treatment by UASB reactor system with anaerobic granular sludge

Textile wastewaters generated from different stages of textile processing contain various toxicants orpollutants that are seriously harmful to natural aquatic environment when released without propertreatment. Although there are different methods, which can be adopted for the treatment of textilewastewater. biological approaches are considered as environmentally friendly, low cost and effectivemethods over other physico-chemical methods. In the present study, simulated textile wastewater(STW) prepared by mixing of three popular acid dyes (Acid blue 204, Acid red 131 and Acid yellow79) in synthetic wastewater was studied for the decolourization and removal of degradable organic inthe laboratory scale Upflow Anaerobic Sludge Blanket Reactor system with anaerobic granular sludgefor about five months at different organic and dye loading rates. The colour removal mechanismsunder .maerobic treatment were also examined since microbial colour removal occurs basically in twoways namely biological degradation, which is more important in textile wastewater treatment, andadsorption of dye molecules onto microbial biomass. Chemical oxygen demand (COD) removal ofacid red 131 (AR 131) containing STW was about 80% at 300 mg/l dye concentration and it was over89% in acid yellow 79 (AY79) dye containing STW under studied conditions. Although acid blue 204(AB204) showed a little inhibition over rnethanogenic consortia, about 93% of COD removal wasobserved at 100 mg/l dye concentration. Colour removal of AR 131 dye containing STW was 95% and.it was credited to biodegradation. Treatment of STW prepared using AY79 showed 95% colourremoval owing to biodegradation while AB204 was quite resistant to biodegradation by anaerobicrn icroorgan isms. Observed colour removal was merely due to the adsorption of dyes onto microbialgranules. Even though a little accumulation of volatile fatty acid (YFA) was observed in increaseddye concentrations, the detected values ofYFA, alkalinity and pH showed that those values were inthe range of desirable limits of anaerobic process. It seems that AR 131 and AY79 can be decolourizedalmost completely by UASB reactor system while AB204 cannot be decolourised since all colourremoval attributed to adsorption of dye onto microbial granules. It can be concluded that anaerobictechnology can be used for the treatment of textile wastewater containing different dyes as an alternativemethod over other methods. However, further study ofUASB reactor for the treatment of real textilewastewater is suggested to find out matrix effect of other chemicals present in real textile wastewaterbefore application to the real world situations

Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment

Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL patients over three consecutive days. The patients received 10 mg arsenic trioxide each day via intravenous infusion. The saliva samples were analyzed using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. Monomethylarsonous acid and monomethylmonothioarsonic acid were identified along with arsenite, dimethylarsinic acid, monomethylarsonic acid, and arsenate. Arsenite was the predominant arsenic species, accounting for 71.8 % of total arsenic in the saliva. Following the arsenic infusion each day, the percentage of methylated arsenicals significantly decreased, possibly suggesting that the arsenic methylation process was saturated by the high doses immediately after the arsenic infusion. The temporal profiles of arsenic species in saliva following each arsenic infusion over 3 days have provided information on arsenic exposure, metabolism, and excretion. These results suggest that saliva can be used as an appropriate clinical biomarker for monitoring arsenic species in APL patients. [Figure: see text

The impact of food additives, artificial sweeteners and domestic hygiene products on the human gut microbiome and its fibre fermentation capacity

Purpose This study investigated the effect of food additives, artificial sweeteners and domestic hygiene products on the gut microbiome and fibre fermentation capacity. Methods Faecal samples from 13 healthy volunteers were fermented in batch cultures with food additives (maltodextrin, carboxymethyl cellulose, polysorbate-80, carrageenan-kappa, cinnamaldehyde, sodium benzoate, sodium sulphite, titanium dioxide), sweeteners (aspartame-based sweetener, sucralose, stevia) and domestic hygiene products (toothpaste and dishwashing detergent). Short-chain fatty acid production was measured with gas chromatography. Microbiome composition was characterised with 16S rRNA sequencing and quantitative polymerase chain reaction (qPCR). Results Acetic acid increased in the presence of maltodextrin and the aspartame-based sweetener and decreased with dishwashing detergent or sodium sulphite. Propionic acid increased with maltodextrin, aspartame-based sweetener, sodium sulphite and polysorbate-80 and butyrate decreased dramatically with cinnamaldehyde and dishwashing detergent. Branched-chain fatty acids decreased with maltodextrin, aspartame-based sweetener, cinnamaldehyde, sodium benzoate and dishwashing detergent. Microbiome Shannon α-diversity increased with stevia and decreased with dishwashing detergent and cinnamaldehyde. Sucralose, cinnamaldehyde, titanium dioxide, polysorbate-80 and dishwashing detergent shifted microbiome community structure; the effects were most profound with dishwashing detergent (R2 = 43.9%, p = 0.008) followed by cinnamaldehyde (R2 = 12.8%, p = 0.016). Addition of dishwashing detergent and cinnamaldehyde increased the abundance of operational taxonomic unit (OTUs) belonging to Escherichia/Shigella and Klebsiella and decreased members of Firmicutes, including OTUs of Faecalibacterium and Subdoligranulum. Addition of sucralose and carrageenan-kappa also increased the abundance of Escherichia/Shigella and sucralose, sodium sulphite and polysorbate-80 did likewise to Bilophila. Polysorbate-80 decreased the abundance of OTUs of Faecalibacterium and Subdoligranulum. Similar effects were observed with the concentration of major bacterial groups using qPCR. In addition, maltodextrin, aspartame-based sweetener and sodium benzoate promoted the growth of Bifidobacterium whereas sodium sulphite, carrageenan-kappa, polysorbate-80 and dishwashing detergent had an inhibitory effect. Conclusions This study improves understanding of how additives might affect the gut microbiota composition and its fibre metabolic activity with many possible implications for human health