关键词： microRNA   alternative splicing   cancer   tissue differentiation   SR proteins   hnRNPs   PTBP1   PTBP2   RBFOX   Quaking   CELF   C. elegans  

摘要： Alternative RNA splicing is an important regulatory process used by genes to increase their diversity. This process is mainly executed by specific classes of RNA binding proteins that act in a dosage-dependent manner to include or exclude selected exons in the final transcripts. While these processes are tightly regulated in cells and tissues, little is known on how the dosage of these factors is achieved and maintained. Several recent studies have suggested that alternative RNA splicing may be in part modulated by microRNAs (miRNAs), which are short, non-coding RNAs (~22 nt in length) that inhibit translation of specific mRNA transcripts. As evidenced in tissues and in diseases, such as cancer and neurological disorders, the dysregulation of miRNA pathways disrupts downstream alternative RNA splicing events by altering the dosage of splicing factors involved in RNA splicing. This attractive model suggests that miRNAs can not only influence the dosage of gene expression at the post-transcriptional level but also indirectly interfere in pre-mRNA splicing at the co-transcriptional level. The purpose of this review is to compile and analyze recent studies on miRNAs modulating alternative RNA splicing factors, and how these events contribute to transcript rearrangements in tissue development and disease.

关键词： Vehicle routing problem   Alternative fuel vehicles   Mixed integer linear programming   Fueling pump reservation  

摘要： The Green Vehicle Routing Problem with Capacitated Alternative Fuel Stations assumes that, at each station, the number of vehicles simultaneously refueling cannot exceed the number of available pumps. The state-of-the-art solution method, based on the generation of all feasible non-dominated paths, performs well only with up to 2 pumps. In fact, it needs cloning the paths between every pair of pumps. To overcome this issue, in this paper, we propose new path-based MILP models without cloning paths, for both the scenario with private stations (i.e., owned by the fleet manager) and that with public stations. Then, a more efficient cutting plane approach is designed for addressing both the scenarios. Numerical results, obtained considering a set of benchmark instances ad hoc generated for this work, show both the efficiency and the effectiveness of this new cutting plane approach proposed. Finally, a sensitivity analysis, carried out by varying the number of customers to be served and their distribution, shows very good performances of the proposed approach.

关键词： alternative reproductive tactics   fisheries-induced evolution   frequency-dependent selection   salmon   simulation   sneaker male  

摘要： Alternative reproductive tactics, where members of a population exhibit divergent mating approaches, are widespread in fishes. The maintenance of such polymorphisms is often explained using game-theoretic concepts such as frequency-dependent selection, which typically assume populations are at equilibrium. However, fish populations exhibit stochastic variability that is inconsistent with the assumption of equilibrium dynamics. We explored how stochastic population dynamics interact with sexual and harvest-induced selection to shape the frequencies of alternative male phenotypes in Pacific salmon (Oncorhynchus spp., Salmonidae). Males of several salmon species are composed of typical "hooknoses" that compete on the spawning grounds for mating opportunities, and rarer "jacks" that mature younger and at smaller sizes to attempt reproduction by "sneaking." Using stochastic simulations, we found that realistic levels of recruitment variation could increase the prevalence of jacks relative to equilibrium expectations. This result is attributable to the "cohort mismatch" phenomenon, whereby differences in age at maturity between male phenotypes cause jacks from strong recruitments to spawn in the same year as hooknoses from weaker cohorts, elevating the proportion of jacks among spawners. Simulations were supported by data from major populations of sockeye salmon (O. nerka, Salmonidae) throughout their North American range, which indicated a positive association between recruitment variability and jack prevalence in some regions. Moreover, we found that frequency-dependent mating dampened population responses to fisheries-induced selection. Our findings emphasize that stochastic ecological processes are important to the maintenance of alternative life histories and interact with selection to produce emergent dynamics that have not previously been recognized.

关键词： equine   fertility   miniature horse   reproduction  

摘要： Pregnancy rates after embryo transfer (ET) are disappointing in donkey species. This study aims to report two successful ET of mini-donkey embryos using Brazilian Northeastern jennies as recipients. Eighteen embryo flushes were performed 9 days post-ovulation in two non-pregnant mini-donkeys jennies (11 and 7 cycles per jenny). Eleven embryos (61%, 11/18) were collected and transferred to Brazilian Northeastern jennies 4-6 days post-ovulation by conventional (n = 6) or an alternative (n = 5) technique. The alternative method consisted of inserting a Polansky equine vaginal speculum smeared with lubricant in the vagina of the recipient jenny. The arms of the speculum were extended to allow the visualization of the cervix. Then, using an adapted crafted, elongated, toothed tissue grasping forceps, the external cervical os was held, and the cervix was gently pulled backward, aiming to straight the cervical canal. The ET gun was inserted through the vagina and cervix by visual inspection, and the embryo was released into the uterine lumen. All embryos collected were Grade 1 and classified as Expanded Blastocysts. No jennies become pregnant after conventional ET (0/6), whereas two recipient jennies (40%, 2/5) become pregnant and delivered offspring in the following year after ET using the alternative technique. In conclusion, Brazilian Northeastern jennies can be used as embryo recipients using the alternative method proposed in the present study. However, further investigations are needed to improve the knowledge and results of ET in donkey species.

关键词： methionine restriction   cysteine restriction   mass spectrometry   LC/MS   cancer therapy   caloric restriction   homocysteine   amino acid analogues   cysteine synthase inhibitor  

摘要： Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a single amino acid in the diet is difficult. However, the in vivo turnover rate of cysteine is usually higher than the rate of intake through food. For this reason, every cell can enzymatically synthesize cysteine from methionine, which enables the use of specific enzymatic inhibitors. In this work, we analysed the potential of cysteine restriction (CysR) in the murine cell line L929. This study determined metabolic fingerprints using mass spectrometry (LC/MS). The profiles were compared with profiles created in an earlier work under MetR. The study was supplemented by proliferation studies using D-amino acid analogues and inhibitors of intracellular cysteine synthesis. CysR showed a proliferation inhibition potential comparable to that of MetR. However, the metabolic footprints differed significantly and showed that CysR does not induce classic LEM at the metabolic level. Nevertheless, CysR offers great potential as an alternative for decisive interventions in general and tumour metabolism at the metabolic level.

关键词： DICER1   pleuropulmonary blastoma   Sertoli-Leydig cell tumor   thoracic tumor  

摘要： A 2-year-old boy presented with a large cystic and solid chest mass arising from the lung, radiographically consistent with pleuropulmonary blastoma (PPB). He underwent right lower lobectomy with resection of a well-circumscribed, mixed solid and cystic mass. The solid areas were composed of cords and nests of tumor cells in the myxoid stroma and retiform foci whose pathologic and immunophenotypic findings were consistent with a sex cord-stromal tumor with features of a Sertoli-Leydig cell tumor. Tumor testing showed a pathogenic variant in the DICER1 RNase IIIb hotspot domain. Family history was suggestive of DICER1 germline pathogenic DICER1 variation in absence of a detectable germline variant. He received 12 cycles of chemotherapy with ifosfamide, vincristine, dactinomycin and doxorubicin (IVADo) and surgery with complete response. One year after completion of chemotherapy, imaging studies showed concern for recurrence confirmed by thorascopic biopsy of a pleural-based mass. He is currently receiving cisplatin-based chemotherapy with reduction in tumor size. Review of the literature showed no similar cases;however, review of our pathology files revealed a single similar case of anterior mediastinal Sertoli cell tumor in a 3-year-old girl.

关键词： Emulsion   Sustainable protein   Green production   Polydispersity index   Stability  

摘要： The search for new sustainably produced food sources and nutritional-value compounds is one of the foremost challenges in food research. To meet this challenge bio-compounds within microalgae have been explored as a sustainable, vegan emulsifier alternative. We hypothesized that proteins extracted from the microalga Scenedesmus obliquus show an ability to emulsify. Hence, the objective of the present study was to evaluate the formation and stability of emulsions containing powdered S. obliquus protein concentrate (SoPC), and the emulsions' resistance to changes in pH value and ionic strength. Dispersions of SoPC were prepared at different protein concentrations (0.1, 0.3, and 0.5% w/w) and pH value (2.5, 5, 7, and 10), stored for 30 days at room temperature (25 +/- 1 degrees C), and evaluated for stability. The hydrodynamic droplet diameters, macroscopic destabilization, creaming index, and polydispersity of the emulsions revealed that 0.5% w/w SoPC was sufficient to produce stable emulsions, even at the most distant pH value (10) from the isoelectric point (2.5). Emulsions prepared with 0.5% SoPC at pH 7 were subjected to stress conditions at pH levels between 2.0 and 9.0, and salinity up to 500 mM NaCl. After eight storage days, emulsions showed resistance to pH stress in the 5.0 to 9.0 range, remained stable at high saline concentrations (<500 mM of NaCl), and were destabilized only close to the protein pI. Soy and whey proteins were destabilized in the pH range of 4.0 to 6.0 and ionic strength above 100 mM. Consequently, S. obliquus proteins at low concentrations formed stable emulsions that were resistant to pH values variation and the presence of salts, indicating that it is a potential sustainable alternative emulsifier with application in the food industry.

关键词： density peak clustering   microheterogeneity   3 ' end sequencing   polyadenylation  

摘要： The dynamic choice of different polyadenylation sites in a gene is referred to as alternative polyadenylation, which functions in many important biological processes. Large-scale messenger RNA 3 ' end sequencing has revealed that cleavage sites for polyadenylation are presented with microheterogeneity. To date, the conventional determination of polyadenylation site clusters is subjective and arbitrary, leading to inaccurate annotations. Here, we present a weighted density peak clustering method, QuantifyPoly(A), to accurately quantify genome-wide polyadenylation choices. Applying QuantifyPoly(A) on published 3 ' end sequencing datasets from both animals and plants, their polyadenylation profiles are reshaped into myriads of novel polyadenylation site clusters. Most of these novel polyadenylation site clusters show significantly dynamic usage across different biological samples or associate with binding sites of trans-acting factors. Upstream sequences of these clusters are enriched with polyadenylation signals UGUA, UAAA and/or AAUAAA in a species-dependent manner. Polyadenylation site clusters also exhibit species specificity, while plants ones generally show higher microheterogeneity than that of animals. QuantifyPoly(A) is broadly applicable to any types of 3 ' end sequencing data and species for accurate quantification and construction of the complex and dynamic polyadenylation landscape and enables us to decode alternative polyadenylation events invisible to conventional methods at a much higher resolution.

关键词： boronizing (boriding)   iron borides   alternative model   kinetics   activation energy  

摘要： An alternative kinetic model is suggested for analyzing the growth of iron boride layers on the surface of steel AISI 316 in the range of 1123 - 1273 K. The approach is based on classical Fick's laws with allowance for the effect of the incubation period on the process of formation of boride layers. The activation energy of boron is calculated for FeB and Fe2B and compared to published data. The model is verified experimentally for the case of 3-h and 5-h boriding at 1243 K. The experimental thicknesses of the layers are compared to the values predicted by the alternative diffusion model and by the integral method. The experimental and the predicted values agree well.

关键词： Poisonous plant   Fetal development   Daily doses   Gestation   Rodent administration  

摘要： L-mimosine is a compound found in Leucaena leucocephala, that is used as animal feed due to its high protein content, but it can also cause intoxication. Due to its low solubility in organic and aqueous solvents, its administration in laboratory animals is difficult, especially in delicate periods such as pregnancy. Thus, to circumvent such problems, this study proposes a stress-free form of oral administration with gelatin tablets with flavoring (meat broth) for 14 consecutive days of the gestational period (GD06 to GD20). For that, 17 pregnant Wistar rats divided into 3 groups were used: control (CO;n = 5) not treated;gelatin (GEL;n = 6), which received a gelatin tablet with flavoring;and gelatin with flavoring added 140 mg/kg of L-mimosine (GM;n = 6). All animals received feed and water ad libitum. The parameters analyzed were body weight gain, water and feed consumption, serum biochemistry, blood count and reproductive indices. Among these, only the real and total weight gains of dams showed statistically significant differences, with a decrease in the group GM. Thus, we could observe that flavored gelatin was an efficient and effective administration method to insoluble compounds and long-term administration to pregnant rats, with quick adaptation and without refusal by the animals. In addition, we could observe a direct effect of L-mimosine on the animals' weight gain;however, the dose administered was not sufficient to confer maternal and fetal toxicity.