Protein sequence design with deep generative models

Protein engineering seeks to identify protein sequences with optimized properties. When guided by machine learning, protein sequence generation methods can draw on prior knowledge and experimental efforts to improve this process. In this review, we highlight recent applications of machine learning to generate protein sequences, focusing on the emerging field of deep generative methods.     

A cost-effective technique for cardiac sparing with deep inspiration-breath hold (DIBH)

Deep inspiration breath hold (DIBH) is an effective technique to reduce cardiac and pulmonary dose during breast radiotherapy (RT). However, as a result of expense and the technical challenges of program implementation, DIBH has not been widely adopted in clinical practice.This report describes a program for DIBH this is relatively inexpensive to implement and has little impact on patient throughput. Multiple redundant mechanisms are incorporated to assure accurate and safe delivery of RT during DIBH. Laser alignment verifies that chest wall excursion is reliably reproduced and maintained during treatment. Chest wall excursion is also monitored independently using an infrared camera trained on a reflective marker on the chest wall. This system automatically triggers “beam off” in the event of movement of the target beyond pre-determined thresholds. Finally, physician review of cine imaging obtained during treatment provides an off-line verification of accurate RT delivery. The approach described herein lowers the investment necessary for implementation of DIBH and may facilitate broader adoption of this valuable technique.     

Simulated sequestration of industrial carbon dioxide at a deep-sea site: Effects on species of harpacticoid copepods

One proposal for alleviating global warming is to sequester large amounts of industrial carbon dioxide on the deep-sea floor, but the environmental consequences of sequestration for the animals living in the sediment are poorly known. In an earlier publication, we reported that, during an experimental sequestration off central California (36.378°N, 122.676°W, 3262 m depth), most individuals of our target taxon (the harpacticoid copepods) were killed, but ∼ 20% survived. Because knowledge of which species survived and how they did so could clarify the effects of sequestration on the fauna, we have now identified the individuals from that experiment to species. Although most were adversely affected, species differed significantly in the degree of their susceptibility. Unexpectedly, six species showed no effect and may be resistant. The hypothesis that harpacticoids could escape the effects of carbon dioxide-rich seawater by moving deeper into the seabed was not supported. Exposure to carbon dioxide-rich seawater created partially defaunated areas, but we found no evidence that disturbance-exploiting harpacticoid species invaded during the recovery of the affected area. Because the environmental effects of the carbon dioxide (e.g. unusually acidic pore water) were still present, however, the opportunity for invasion might not yet have occurred. Differences among species in susceptibility increase the complexity of the effects of carbon dioxide sequestration on the deep-sea fauna.     

Fate map and morphogenesis of presumptive neural crest and dorsal neural tube

In contrast to the classical assumption that neural crest cells are induced in chick as the neural folds elevate, recent data suggest that they are already specified during gastrulation. This prompted us to map the origin of the neural crest and dorsal neural tube in the early avian embryo. Using a combination of focal dye injections and time-lapse imaging, we find that neural crest and dorsal neural tube precursors are present in a broad, crescent-shaped region of the gastrula. Surprisingly, static fate maps together with dynamic confocal imaging reveal that the neural plate border is considerably broader and extends more caudally than expected. Interestingly, we find that the position of the presumptive neural crest broadly correlates with the BMP4 expression domain from gastrula to neurula stages. Some degree of rostrocaudal patterning, albeit incomplete, is already evident in the gastrula. Time-lapse imaging studies show that the neural crest and dorsal neural tube precursors undergo choreographed movements that follow a spatiotemporal progression and include convergence and extension, reorientation, cell intermixing, and motility deep within the embryo. Through these rearrangement and reorganization movements, the neural crest and dorsal neural tube precursors become regionally segregated, coming to occupy predictable rostrocaudal positions along the embryonic axis. This regionalization occurs progressively and appears to be complete in the neurula by stage 7 at levels rostral to Hensen's node.     

急性右下肢深静脉血栓的临床治疗分析

目的:探讨右下肢深静脉血栓的临床治疗方法。方法:对我院2015年6月-2017年6月收治的63例右下肢深静脉血栓形成患者进行回顾性分析,从小腿周径差、彩超检查及造影3方面对疗效进行评价,并统计导管接触溶栓后患者复查肺部增强CT情况。结果:63例患者中,57例进行导管接触溶栓+下腔静脉滤器,6例进行导管接触溶栓+下腔静脉滤器+肺动脉碎栓、溶栓。治疗后,患者小腿周径差较治疗前明显降低,差异具有统计学意义(P0.05)。患者显效26例,有效28例,好转8例,无效1例,临床治愈率为85.7%。63例下腔静脉滤器,取出60例,3例留置为永久性滤器。新增肺栓塞12例,无致死性肺栓塞发生。结论:导管接触溶栓对右下肢深静脉血栓的治疗效果较好,但导管接溶栓时有较高肺栓塞发生率,应积极放置下腔静脉滤器。     

不同剂量利伐沙班对老年髋关节置换术患者凝血功能及下肢深静脉血栓的影响

目的:探讨不同剂量利伐沙班对老年髋关节置换术患者凝血功能及下肢深静脉血栓(DVT)的影响。方法:选择2013年6月~2016年6月期间我院收治的200例老年髋关节置换术患者,按随机数字表法分为两组各100例,术后分别予利伐沙班5 mg、10mg口服以预防DVT。术前及术后1d、7d检测纤维蛋白原(Fbg)、凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血酶原时间(APTT)及D-二聚体(D-D),同时行下肢彩色多普勒超声检查判断DVT发生情况,观察临床出血事件。结果:术后1d两组Fbg水平明显降低,PT明显延长(均P0.05);术后7d两组Fbg水平与术后1d相比明显回升,PT明显缩短(均P0.05)。两组各时期的Fbg与PT均无明显差异(P0.05)。术后1d两组D-D水平均明显升高(P0.05),且利伐沙班5 mg组明显高于利伐沙班10 mg组(P0.05);术后7d两组D-D水平均较术后1d明显降低(P0.05),且利伐沙班10 mg组明显低于利伐沙班5 mg组(P0.05)。利伐沙班10 mg组术后早期DVT发生率明显低于利伐沙班5 mg组(P0.05)。两组预防性抗凝后临床出血事件的发生率比较无统计学差异(P0.05)。结论:老年髋关节置换术后口服大剂量(10 mg)利伐沙班,可有效改善血液高凝状态,降低DVT发生率,且不会明显增加临床出血事件,值得推广。     

A new comprehensive method for detection of livestock-related pathogenic viruses using a target enrichment system

We tested usefulness of a target enrichment system SureSelect, a comprehensive viral nucleic acid detection method, for rapid identification of viral pathogens in feces samples of cattle, pigs and goats. This system enriches nucleic acids of target viruses in clinical/field samples by using a library of biotinylated RNAs with sequences complementary to the target viruses. The enriched nucleic acids are amplified by PCR and subjected to next generation sequencing to identify the target viruses. In many samples, SureSelect target enrichment method increased efficiencies for detection of the viruses listed in the biotinylated RNA library. Furthermore, this method enabled us to determine nearly full-length genome sequence of porcine parainfluenza virus 1 and greatly increased Breadth, a value indicating the ratio of the mapping consensus length in the reference genome, in pig samples. Our data showed usefulness of SureSelect target enrichment system for comprehensive analysis of genomic information of various viruses in field samples.     

Circular RNA profiling reveals chi_circ_0008219 function as microRNA sponges in pre-ovulatory ovarian follicles of goats (Capra hircus)

Circular RNAs (circRNAs) are a new class of non-coding RNAs in animals and are a novel target of non-coding RNA (ncRNA) regulation. The mechanism and function of circRNAs have been reported in some species and tissues. However, there is little available information on the functions of circRNAs in the goat reproductive system. In the present study, we deeply sequenced and analyzed circRNAs through bioinformatics to reveal the expression profiles, and predicted 13,950 circRNAs in the pre-ovulatory ovarian follicles of goats for the first time. Thirty-seven circRNAs were differentially expressed in the Boer goat compared with the Macheng black goat. The chi_circ_0008219 was involved in a vast circRNA-miRNA-mRNA co-expression network. Via a luciferase activity assay, chi_circ_0008219 is observed to sponge to 3 ovarian follicle-related miRNAs. These findings demonstrate that circRNAs have potential effects in the ovarian follicles of ewes and may represent a promising new research field in ovarian follicular development.     

Maximum rooting depth of vegetation types at the global scale

The depth at which plants are able to grow roots has important implications for the whole ecosystem hydrological balance, as well as for carbon and nutrient cycling. Here we summarize what we know about the maximum rooting depth of species belonging to the major terrestrial biomes. We found 290 observations of maximum rooting depth in the literature which covered 253 woody and herbaceous species. Maximum rooting depth ranged from 0.3 m for some tundra species to 68 m for Boscia albitrunca in the central Kalahari; 194 species had roots at least 2 m deep, 50 species had roots at a depth of 5 m or more, and 22 species had roots as deep as 10 m or more. The average for the globe was 4.6±0.5 m. Maximum rooting depth by biome was 2.0±0.3 m for boreal forest. 2.1±0.2 m for cropland, 9.5±2.4 m for desert, 5.2±0.8 m for sclerophyllous shrubland and forest, 3.9±0.4 m for temperate coniferous forest, 2.9±0.2 m for temperate deciduous forest, 2.6±0.2 m for temperate grassland, 3.7±0.5 m for tropical deciduous forest, 7.3±2.8 m for tropical evergreen forest, 15.0±5.4 m for tropical grassland/savanna, and 0.5±0.1 m for tundra. Grouping all the species across biomes (except croplands) by three basic functional groups: trees, shrubs, and herbaceous plants, the maximum rooting depth was 7.0±1.2 m for trees, 5.1±0.8 m for shrubs, and 2.6±0.1 m for herbaceous plants. These data show that deep root habits are quite common in woody and herbaceous species across most of the terrestrial biomes, far deeper than the traditional view has held up to now. This finding has important implications for a better understanding of ecosystem function and its application in developing ecosystem models.