Exploration of Genome-Wide Recombination Rate Variation Patterns at Different Scales in Pigs.

Meiotic recombination is a prevalent process in eukaryotic sexual reproduction organisms that plays key roles in genetic diversity, breed selection, and species evolution. However, the recombination events differ across breeds and even within breeds. In this study, we initially computed large-scale population recombination rates of both sexes using approximately 52 K SNP genotypes in a total of 3279 pigs from four different Chinese and Western breeds. We then constructed a high-resolution historical recombination map using approximately 16 million SNPs from a sample of unrelated individuals. Comparative analysis of porcine recombination events from different breeds and at different resolutions revealed the following observations: Firstly, the 1Mb-scale pig recombination maps of the same sex are moderately conserved among different breeds, with the similarity of recombination events between Western pigs and Chinese indigenous pigs being lower than within their respective groups. Secondly, we identified 3861 recombination hotspots in the genome and observed medium- to high-level correlation between historical recombination rates (0.542~0.683) and estimates of meiotic recombination rates. Third, we observed that recombination hotspots are significantly far from the transcription start sites of pig genes, and the silico-predicted PRDM9 zinc finger domain DNA recognition motif is significantly enriched in the regions of recombination hotspots compared to recombination coldspots, highlighting the potential role of PRDM9 in regulating recombination hotspots in pigs. Our study analyzed the variation patterns of the pig recombination map at broad and fine scales, providing a valuable reference for genomic selection breeding and laying a crucial foundation for further understanding the molecular mechanisms of pig genome recombination.

Recombination map construction method using ONT sequence.

Although meiotic recombination is a key step shared by eukaryotes, the rate of recombination varies at different taxonomic levels. The construction of high-resolution genome-wide recombination maps will help us understand the variability patterns of recombination rates and their molecular basis. ONT sequencing technology has the characteristics of long read length, high throughput, and reasonable cost, and can be used as a data source for the construction of whole-gene recombination landscapes. In order to construct the genome-wide recombination map of an individual conveniently and accurately, we developed a method to construct the recombination landscape based on the third-generation sequencing technology, Oxford Nanopore Sequencing. Here we detail a step-by-step approach to efficiently and accurately construct genome-wide recombination maps using ONT pooled sequencing data. The main contents include compression homopolymers and alignment; acquisition of high-quality variants; estimation of recombinant molecules by the sliding window method; and construction of recombinant maps. The results of simulation data validation show that our method has high sensitivity and specificity at moderate heterozygous variant density and sequencing depth. This method provides a new way of constructing high-resolution individual genome recombination maps using long read sequences, and has important reference significance for the study of recombination rate variation.

Quantification and visualization of meat quality traits in pork using hyperspectral imaging.

Accurate and rapid determination of meat quality traits plays key roles in food industry and pig breeding. Currently, most of the spectroscopic instruments developed for meat quality determination can only obtain the spectral average value of the sample, so it is difficult to evaluate the spatial variation of meat quality traits. In this study, we evaluated the predictive potential of 14 meat quality traits based on large-scale VIS/NIR hyperspectral images collected by SpecimIQ. When predictions were based solely on hyperspectral data, the prediction accuracy (R2cv) for the majority of meat qualities ranged from 0.60 to 0.70. After adding texture information, the prediction accuracy of all traits is improved by different magnitudes (R2cv increases from 1.5% to 16.4%). Finally, the best model was utilized to visualize the spatial distribution of Fat (%) and Moisture (%) to assess their homogeneity. These results suggest that hyperspectral imaging has great potential for predicting and visualizing various meat qualities, as well as industrial applications for automated measurements.

NanoCross: A pipeline that detecting recombinant crossover using ONT sequencing data.

Meiotic recombination is crucial for eukaryotes but varies among taxonomic scales (between individuals, groups, species, etc.) and genome resolutions. Studying how and why recombination rates change can help us understand the molecular basis and mechanisms of genetics and evolution. We introduce a genome-wide identification script called NanoCross, which uses ONT sequences to detect pooled gamete DNA cross recombination events. NanoCross first reduced sequencing errors and then constructed individual haplotypes based on homopolymer-filtered ONT sequences. Then, each molecule read is used to estimate cross recombination. In the case of moderate heterozygous variation density and sequencing depth, simulations revealed that our technique offers a good level of sensitivity and specificity. We constructed a high-resolution recombination map of wild boar genomes using NanoCross and compared it to recombination maps of male breeding pig populations. NanoCross provides us with a method and scripts for constructing a high-resolution individual genome recombination map utilizing long-read sequencing, as well as a novel approach for examining the variation in individual recombination rate. The source code and data mechanism are hosted on GitHub (https://github.com/zuoquanchen/NanoCross).

Extensive evaluation of prediction performance for 15 pork quality traits using large scale VIS/NIRS data.

Visible and near-infrared spectroscopy (VIS/NIRS) has been extensively used in the livestock and food industries to quantify meat quality. Here, we collected VIS/NIRS data of 1206 pigs longissimus muscle, measured the corresponding 15 meat quality traits, and used seven models to predict these meat quality traits. The prediction performances of 7 models varied among predicted traits, with the Rcv2 of most traits above 0.9 in the best model. We have also established a new method, spectral-wide association analysis (SWAS), to select the feature wavelengths of measured traits. Results showed that the prediction performance is proportionate to the number of identified significant association wavelengths. We used the selected wavelengths to perform prediction again, and the prediction accuracy was similar to results with full wavelength using the best model, indicating effectiveness of feature wavelengths selection methods.

Safety of endovascular therapy for symptomatic intracranial artery stenosis: a national prospective registry.

INTRODUCTION: The safety outcomes of endovascular therapy for intracranial artery stenosis in a real-world stetting are largely unknown. The Clinical Registration Trial of Intracranial Stenting for Patients with Symptomatic Intracranial Artery Stenosis (CRTICAS) was a prospective, multicentre, real-world registry designed to assess these outcomes and the impact of centre experience. METHODS: 1140 severe, symptomatic intracranial arterial stenosis (ICAS) patients treated with endovascular therapy were included from 26 centres, further divided into three groups according to the annual centre volume of intracranial angioplasty and stent placement procedures over 2 years: (1) high volume for ≥25 cases/year; (2) moderate volume for 10-25 cases/year and (3) low volume for <10 cases/year. RESULTS: The rate of 30-day stroke, transient ischaemic attack or death was 9.7% (111), with 5.4%, 21.1% and 9.7% in high-volume, moderate-volume and low-volume centres, respectively (p<0.05). Multivariable logistic regression confirmed high-volume centres had a significantly lower primary endpoint compared with moderate-volume centres (OR=0.187, 95% CI: 0.056 to 0.627; p≤0.0001), while moderate-volume and low-volume centres showed no significant difference (p=0.8456). CONCLUSION: Compared with the preceding randomised controlled trials, this real-world, prospective, multicentre registry shows a lower complication rate of endovascular treatment for symptomatic ICAS. Non-uniform utilisation in endovascular technology, institutional experience and patient selection in different volumes of centres may have an impact on overall safety of this treatment.

FMixFN: A Fast Big Data-Oriented Genomic Selection Model Based on an Iterative Conditional Expectation algorithm.

Genomic selection is an approach to select elite breeding stock based on the use of dense genetic markers and that has led to the development of various models to derive a predictive equation. However, the current genomic selection software faces several issues such as low prediction accuracy, low computational efficiency, or an inability to handle large-scale sample data. We report the development of a genomic prediction model named FMixFN with four zero-mean normal distributions as the prior distributions to optimize the predictive ability and computing efficiency. The variance of the prior distributions in our model is precisely determined based on an F2 population, and genomic estimated breeding values (GEBV) can be obtained accurately and quickly in combination with an iterative conditional expectation algorithm. We demonstrated that FMixFN improves computational efficiency and predictive ability compared to other methods, such as GBLUP, SSgblup, MIX, BayesR, BayesA, and BayesB. Most importantly, FMixFN may handle large-scale sample data, and thus should be able to meet the needs of large breeding companies or combined breeding schedules. Our study developed a Bayes genomic selection model called FMixFN, which combines stable predictive ability and high computational efficiency, and is a big data-oriented genomic selection model that has potential in the future. The FMixFN method can be freely accessed at https://zenodo.org/record/5560913 (DOI: 10.5281/zenodo.5560913).

Using overlapping low-profile visualized intraluminal support stent-assisted coil embolization for treating blood blister-like aneurysms of the internal carotid artery.

Blood blister-like aneurysm (BBA) of the internal carotid artery (ICA) is highly challenging to treat owing to its variable morphology and tendency for rupture and regrowth. In this study, we attempted to discuss the key techniques for overlapping low-profile visualized intraluminal support (LVIS) stent-assisted coil embolization, which is used for treating BBAs in our center. Clinical characteristics, endovascular treatment details, outcomes, and follow-up results of 13 patients with BBA treated at our center were retrospectively evaluated in this study. Overlapping LVIS stent-assisted coil embolization was successfully performed in all 13 patients of ruptured BBAs located in the ICAs. Recurrence of aneurysm was observed in 4 cases (30.8%) during the angiographic follow-up; in 2 of these cases, spontaneous healing was observed after discontinuation of antiplatelet therapy. Further, 2 patients with recurrence underwent endovascular treatment with complete obliteration of the aneurysm in one and occlusion of the parent artery after Onyx embolization and stent placement in the other. The overall obliteration rate of the BBAs was 92.3% (12/13). One patient (7.7%) developed intraoperative rupture of the aneurysm with coils protruding outside; however, no severe hemorrhage or neurological dysfunction occurred owing to timely embolization. Overlapping LVIS stent-assisted coil embolization is effective for management of BBA of the ICA. Appropriate adjustment in antiplatelet therapy may improve healing in recurrent cases.

S100A12 promotes inflammation and apoptosis in ischemia/reperfusion injury via ERK signaling in vitro study using PC12 cells.

S100A12 is a member of S100 calcium-binding proteins with effect to promote inflammation in brain damage and stroke. However, the role of S100A12 in ischemia/reperfusion (I/R) remains to be clarified. This study aimed to explore the effect of S100A12 on I/R and discover the possible mechanism. Oxygen-glucose deprivation and reperfusion (OGD/R) was used to induce I/R injury model in vitro. Knockdown or overexpression of S100A12 was utilized to explore the role of S100A12 in I/R-induced inflammation and apoptosis. Results indicated that S100A12 expression was dramatically upregulated after OGD/R. Knockdown of S100A12 inhibited, while overexpression of S100A12 enhanced, the activation of ERK1/2 protein. OGD/R also triggered the occurrence of inflammation and oxidative stress, while these effects were blunted by S100A12 silencing and aggravated by S100A12 overexpression, and the presence of MAP kinase signaling system (ERK) inhibitor MK-8353 counteracted the effect of S100A12 overexpression. Besides, S100A12 silencing abolished, while its overexpression restored, the OGD/R-induced increased apoptosis rate and pro-apoptotic proteins expression. Similarly, ERK inhibitor MK-8353 reversed the effects of S100A12 overexpression. In conclusion, S100A12 promoted OGD/R-induced inflammation, oxidative stress and apoptosis via activation of ERK signaling in vitro.

Medical and Interventional Therapy for Spontaneous Vertebral Artery Dissection in the Craniocervical Segment.

Background and Purpose. Spontaneous vertebral artery dissection (SVAD) is an important reason for posterior-circulation-ischemic stroke in the young and middle-aged population. Although some previous reports reveal a favorable outcome with conservative therapy, it is still controversial in the treatment of SVAD in some specific patients. Herein, we present our 10 years of clinical experience for SVAD at this location. Material and Methods. 20 patients with 20 SVADs in V2 and V3 segments were retrospectively studied. Clinical manifestations and imageology materials were collected and analyzed. All the patients underwent anticoagulation except for one patient because of contraindication. 14 patients underwent Wingspan stents implantation with general anesthesia. Results. In our sample, ischemia (infarction or transient ischemic attack, TIA) was found in all the patients. Angiographic stenosis and dissection aneurysm were the most common findings in the segments mentioned above. 19 of the patients (95%) got the excellent imageological and clinical outcomes. Conclusions. According to our experience in this group, although anticoagulation is effective in vertebral artery dissection, interventional therapy for SVADs in V2 and/or V3 segments is preferred in some specific patients. Stent with higher radial supporting and flexibility, such as Wingspan stent, is suggested.

Combined use of Onyx and coils for transarterial balloon-assisted embolization of traumatic carotid-cavernous fistulas: a report of 16 cases with 17 fistulas.

OBJECTIVE: The combination of coils and Onyx for the treatment of carotid-cavernous fistulas (CCFs) is an interesting new development. The purpose of the current study is to evaluate our preliminary experience with the combined use of coils and Onyx for the treatment of traumatic CCFs. METHODS: Between April 2009 and July 2014, 16 patients with 17 traumatic CCFs were embolized with the so-called 'armored concrete' treatment modality using coils, Onyx-18, and a non-detachable balloon via the transarterial approach. The outcomes were assessed both clinically and radiologically. Digital subtraction angiography (DSA) follow-up was performed 3 or 6 months after endovascular treatment while clinical follow-up was continued until December 2014. RESULTS: Obliteration of the CCFs was obtained with patency of the parent artery in all 16 cases. Follow-up DSA demonstrated stable occlusion of all the fistulas. Symptoms related to the CCFs were either resolved immediately or gradually over 2 months. No worsening of the cranial neuropathies was observed during the follow-up period which averaged 32.6 months. CONCLUSIONS: The 'armored concrete' treatment modality using coils, Onyx, and a non-detachable balloon promises to be a safe, economical, and effective alternative in the management of traumatic CCFs.

Management of consecutive development of ruptured intracranial mycotic aneurysms: case report.

Intracranial mycotic aneurysm (MA), also known as intracranial infectious aneurysm, is a rare type of intracranial aneurysm. However, it carries a high mortality rate of 80% when ruptured and 30% even when unruptured. Here we report a 22-year-old male patient who consecutively developed two ruptured intracranial MAs related to infective endocarditis. The time interval between the two attacks was approximately seven months. The second aneurysm formed and ruptured regardless of long-term antibiotic therapy and cardiac surgery to replace the dysfunctional aortic valve. This case indicates that intracranial MAs may develop even after successful treatment of the underlying cardiac disorders, and hence close angiographic follow-ups may be warranted following the cardiac surgery.

Screening and functional analysis of glioma­related genes induced by candoxin.

This study aimed to identify time­specific and common differential genes (CDGs) expressed in glioma cells following exposure to candoxin at three different time­points. Gene expression data from candoxin­treated human glioma (Hs 683) cells were downloaded from the Gene Expression Omnibus database (accession number, GSE1682), from a 12­time­point set of samples. Differentially expressed genes were screened between control and candoxin­treated samples at different time­points, and three time­specific gene sets and CDGs were identified. All genes were subject to pathway enrichment analysis to gain further insight into gene function. CDGs were clustered based upon their original expression between 0 and 48 h, and, from this subset, feature genes were selected. Small molecules associated with candoxin were identified by comparing the expression pattern of the most valid candidate genes with that of differential genes exposed to small molecules in the Connectivity Map. From the 12­, 24­ and 48­h time­points, 746, 265 and 539 differentially expressed genes were identified, respectively. A total of 129 genes were differentially expressed and significantly enriched in focal adhesion and gap junction pathways. From these, 11 feature genes and one marker gene (EPS8L1) were identified. Four small molecules that were most relevant to candoxin action were identified. In conclusion, it is hypothesized that candoxin stimulation can cause glial inflammation through mutations in cell adhesion activity. The EPS8L1 gene may be a valid marker for glioma diagnosis, and the four small molecules identified may be relevant for future drug design.

A novel intravital method to evaluate cerebral vasospasm in rat models of subarachnoid hemorrhage: a study with synchrotron radiation angiography.

Precise in vivo evaluation of cerebral vasospasm caused by subarachnoid hemorrhage has remained a critical but unsolved issue in experimental small animal models. In this study, we used synchrotron radiation angiography to study the vasospasm of anterior circulation arteries in two subarachnoid hemorrhage models in rats. Synchrotron radiation angiography, laser Doppler flowmetry-cerebral blood flow measurement, [(125)I]N-isopropyl-p-iodoamphetamine cerebral blood flow measurement and terminal examinations were applied to evaluate the changes of anterior circulation arteries in two subarachnoid hemorrhage models made by blood injection into cisterna magna and prechiasmatic cistern. Using synchrotron radiation angiography technique, we detected cerebral vasospasm in subarachnoid hemorrhage rats compared to the controls (p<0.05). We also identified two interesting findings: 1) both middle cerebral artery and anterior cerebral artery shrunk the most at day 3 after subarachnoid hemorrhage; 2) the diameter of anterior cerebral artery in the prechiasmatic cistern injection group was smaller than that in the cisterna magna injection group (p<0.05), but not for middle cerebral artery. We concluded that synchrotron radiation angiography provided a novel technique, which could directly evaluate cerebral vasospasm in small animal experimental subarachnoid hemorrhage models. The courses of vasospasm in these two injection models are similar; however, the model produced by prechiasmatic cistern injection is more suitable for study of anterior circulation vasospasm.

Establishment of a novel hemodynamic cerebral ischemia model of atherosclerotic rabbit.

BACKGROUND: Atherosclerosis is the most common cause of ischemic stroke. Until now, there has been no ideal animal model for studying the hemodynamic ischemia caused by atherosclerosis in posterior circulation. OBJECTIVE: This study was conducted to establish a cerebral ischemic model in an atherosclerotic rabbit by subclavian artery (SA) ligation or embolization, emphasizing the role of hemodynamics. MATERIALS AND METHODS: Thirty-two male New Zealand rabbits (weight, 3.5 to 4.0 kg; provided by Animal Laboratory of Tongji Hospital of Tongji University) were randomly divided into four groups. All the groups, except the controlled group, were fed with high lipid diet for three months and two of the groups were submitted for right SA ligation or left SA embolization and the remaining one group to non-operated group. RESULTS: A SA steal syndrome was established successfully with delayed visualization and prolonged circulation time in the posterior circulation. The circulation time was different when SA was ligated or embolized (P < 0.001), and also there was statistically significant difference between controlled and non-operated groups when angiography of either, left and right, VA was performed (P = 0.009, P = 0.003, respectively). However, there was no statistical significant difference between the ligation and embolization group either before or after the procedure (ligation or embolization) (P = 0.402, P = 0.068, respectively). In the control and non-operated group, angiography of either left or right VA showed no statistically significant difference (P = 0.285, P = 0.197, respectively). In the groups fed with high lipid diet for three months, atherosclerotic plaques were found in the common carotid arteries (CCAs), aortic arch (AAs) and variably in the internal carotid arteries (ICAs). CONCLUSIONS: This model could, to some extent, simulate the clinical hemodynamic state of atherosclerotic stroke. and it is an ideal model for studying the hemodynamic cerebral ischemia in posterior circulation.

Endovascular embolization of small ruptured intracranial aneurysms using a biplane angiographic system with three-dimensional rotational digital subtraction angiography.

Endovascular coiling of small, ruptured intracranial aneurysms is controversial because of technical difficulties. We analyzed the clinical and angiographic effects of endovascular treatment of 39 small (5mm) ruptured intracranial aneurysms (in 37 patients) at our institution between March 2004 and March 2007. Procedures were carried out on a biplane angiographic system with three-dimensional rotational digital subtraction angiography. Immediately after embolization, 30 aneurysms were completely occluded and nine had a residual neck. The volumetric percentage occlusion was 45.2+/-9.7%. Angiographic and clinical follow-up was at 6.1 months and 15.9 months, respectively. Delayed rebleeding was not observed. Complications directly related to the procedure were encountered in two patients (one coil migration and one intraoperative rupture). For 34 patients, the final outcome was excellent or good, one suffered a moderate disability, one a severe disability and one patient died. The results suggest that endovascular embolization is effective and safe for patients with small ruptured intracranial aneurysms.

Correlation between carotid intraplaque hemorrhage and clinical symptoms: systematic review of observational studies.

BACKGROUND AND PURPOSE: We sought to investigate the association between carotid intraplaque hemorrhage (IPH) and ipsilateral symptoms of cerebral ischemia. METHODS: A search was performed for clinical observational studies comparing the incidence of IPH between symptomatic and asymptomatic patients. Odds ratios (ORs) for IPH as a factor in the pathogenesis of neurologic events were calculated and combined by a meta-analysis. Interstudy heterogeneity, estimated effects, and methodologic quality of the studies were assessed. RESULTS: Thirty-one studies were included for analysis. The reported ORs varied widely. Overall, the incidence of IPH in the symptomatic groups was significantly higher than in the asymptomatic group. However, there was an apparent trend for heterogeneity (P<0.00001) between studies. The random-effects summary estimator of ORs was 2.25 (95% CI, 1.57 to 3.22; P<0.00001). To identify potential sources of heterogeneity, subgroup analyses were performed. The pooled ORs varied greatly by stratification. Major heterogeneity was found among studies with low quality, microscopic methods of examination, significant effects, small sizes, early publication, and unequal severity of carotid stenosis in both groups. Large, recent, macroscopic, or high-quality studies, as well as studies with equal degrees of stenosis, tended to yield insignificant associations. The methods in defining and evaluating hemorrhage were very heterogeneous. Characterizations of the age, size, number, and location of hemorrhages were poorly reported and highly variable. In addition, a lack of control of confounders and selection bias were frequently identified among studies. CONCLUSIONS: Statistical inferences have suggested a plausible role in the production of cerebral ischemia; however, reliable interpretation was strongly undermined by poor methodologic quality, substantial heterogeneity, and suspicious publication bias. To preciously estimate the underlying correlation, a well-designed study with uniformity in definition and evaluation for IPH might be warranted.

The correlation of carotid plaque pathohistologic features and neurological symptoms: a meta-analysis of observational studies.

OBJECTIVE: To investigate the association between the pathological features of carotid plaque and ipsilateral symptoms of cerebral ischemia. MATERIALS AND METHODS: We sought to identify clinical observational studies comparing the incidence of pathological features between symptomatic and asymptomatic carotid plaques in terms of ulceration, thrombosis and intraplaque hemorrhage (IPH), published between 1996 and 2006. A search on, PubMed was supplemented by a review of bibliographies of relevant articles and lists of references in it. Odds ratios (OR) for the presence of each feature as a role in the pathogenesis of neurological events were calculated and combined by a meta-analysis. RESULTS: We integrated 16 clinical studies totaling 2839 plaques harvested at endarterectomy procedures. The reported incidence for each feature was highly variable. The methods in defining ulceration, thrombosis and IPH were very heterogeneous. The time intervals between the latest onset of ischemic symptoms and pathological examinations varied greatly. Overall, the incidence of ulcerated plaques in the symptomatic group were significantly higher than that in the asymptomatic group (study number, n=10; OR, 2.32; 95% CI, 1.90-2.83. A random-effect model was performed among studies regarding surface thrombosis because an apparent trend for heterogeneity was observed (n=6; OR, 1.57; 95% CI, 0.68-3.64). There was no difference with respect to IPH between the two groups (n=11; OR, 1.09; 95% CI, 0.91-1.32). CONCLUSIONS: Ulcerated carotid plaque is significantly correlated with the production of neurological events, whereas thrombosis fails to correlate with ischemic symptoms because of the presence of substantial heterogeneity. The association between IPH and clinical presentations is less clear.