Effects of different stocking densities on the development of reproductive and immune functions in young breeder pigeons during the rearing period.

1. Stocking density (SD) is closely related to animal performance. This experiment was designed to evaluate the development of reproductive and immune functions of young pigeons under different SDs.2. A total of 288 (half male and half female) 40-day-old pigeons (body weight 400 ± 15 g) were allocated into four groups: High stocking density (HSD; 0.308 m3/bird), standard stocking density (SD; 0.616 m3/bird), and low stocking density (LSD; 1.232 m3/bird) and a caged (control; 0.04125 m3/bird). Every group had six replicates of the same sex.3. The results showed that caged male pigeons had the highest testis index, testosterone content, and gene expression of the androgen receptor gene. LSD treatment induced the highest concentrations of oestradiol, progesterone and mRNA levels of reproductive hormone receptor genes in female pigeons. In male pigeons, the spleen index (organ weight calculated as a percentage of total body weight) showed a peak level (0.09 ± 0.020) in the LSD group, and the thymus index peaked (0.23 ± 0.039) in SD group. However, the index for ovary, spleen, thymus and bursa of Fabricius in female pigeons showed no significant changes among different groups.4. The IL-1ß, IL-8, IFN-γ, TGF-ß and toll-like receptor 2 (TLR-2) mRNA levels reached their maximum values in both male and female pigeon spleens in the LSD group.5. Young male pigeons housed in cages showed increased testicular development while low stocking density increased the development of reproductive function in young female pigeons. A larger activity space could help enhance the immune function of both male and female pigeons.

Evaluation of CT angiography obstruction score and pulmonary perfusion defect score using the third-generation dual-source CT for pulmonary embolism.

AIM: To investigate the application value of computed tomography (CT) angiography (CTA) obstruction score and pulmonary perfusion defect score on the third-generation dual-source CT for pulmonary embolism and the changes of the right ventricular function. MATERIALS AND METHODS: The clinical data of 52 patients with pulmonary embolism (PE) confirmed using the third-generation dual-source dual-energy CTPA were analysed retrospectively. These patients were divided into the severe group and non-severe group according to their clinical manifestations. The results of CTPA and dual-energy pulmonary perfusion imaging (DEPI) were recorded by two radiologists for index computation. The ratio of the maximum short-axis diameter of the right ventricle (RV) to that of the left ventricle (LV) was also recorded. The correlation analysis between RV/LV and the mean values of CTA obstruction score and perfusion defect score was performed. Correlation analysis and agreement analysis were performed on the data measured by two radiologists, CTA obstruction score, and pulmonary perfusion defect score. RESULTS: CTA obstruction score and perfusion defect score measured by the two radiologists had good correlation and agreement. CTA obstruction score, perfusion defect score, and RV/LV were significantly lower in the non-severe group than in the severe PE group. RV/LV had a significant positive correlation with CTA obstruction score and perfusion defect score (p<0.05). CONCLUSION: The third-generation dual-source dual-energy CT plays a positive role in assessing PE severity and RV function and can provide additional information for the clinical management and treatment of PE patients.

Expression of ICAM-1 and E-selectin in different metabolic obesity phenotypes: discrepancy for endothelial dysfunction.

OBJECTIVES: Endothelial dysfunction, the earliest vascular alteration, is a consequence of metabolic disorders associated with obesity. However, it is still unclear whether a proportion of obese individuals without metabolic alterations associated with obesity, defined as "metabolically healthy obesity (MHO)", exhibit better endothelial function. We therefore aimed to investigate the association of different metabolic obesity phenotypes with endothelial dysfunction. METHODS: The obese participants without clinical cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis) were allocated to the different metabolic obesity phenotypes based on their metabolic status, including MHO and metabolically unhealthy obesity (MUO). Associations of metabolic obesity phenotypes with the biomarkers of endothelial dysfunction, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin), were evaluated using multiple linear regression models. RESULTS: Plasma levels of sICAM-1 and sE-selectin were respectively measured in 2371 and 968 participants. Compared to the non-obese participants, those with MUO were associated with higher concentrations of sICAM-1 (ß 22.04, 95% CI 14.33-29.75, P < 0.001) and sE-selectin (ß 9.87, 95% CI 6.00-13.75, P < 0.001) after adjusting for confounders. However, no differences were found for the concentrations of sICAM-1 (ß 0.70, 95% CI - 8.91 to 10.32, P = 0.886) and sE-selectin (ß 3.69, 95% CI - 1.13 to 8.51, P = 0.133) in the participants with MHO compared to the non-obese participants. CONCLUSIONS: Individuals with MUO were associated with elevated biomarkers of endothelial dysfunction, but the association with endothelial dysfunction was not found in those with MHO, indicating that the individuals with MHO might exhibit better endothelial function.

Dynamic changes in protein concentrations of keratins in crop milk and related gene expression in pigeon crops during different incubation and chick rearing stages.

1. The objective of this study was to examine the keratin composition of crop milk, the variation of epithelial thickness and keratin (K) gene expression in samples from young pigeon during incubation and chick rearing.2. Crop milk was collected from 1-, 3- and 5-day-old squab crops for keratin content analysis. Results showed that K4 accounted for the highest proportion of all detected keratins.3. In total, 42 pairs of adult pigeons were allocated to seven groups according to different stages to collect crop samples. Gene expression studies showed that the K3 gene expression was maximised at rearing Day 15 (15) and R1 in males and females, respectively. K6a gene level was the greatest at R15 in females, whereas it peaked at incubation Day 4 (I4) in males. The K12, K13, K23 and K80 gene levels were inhibited at the peak period of crop milk formation in comparison with I4. In females, K cochleal expression peaked at I10, whereas it was the greatest at R25 in males. K4 and K14 gene expression was the highest at I10 in females, while K4 and K14 were minimised at I17 and R7 in males, respectively. Gene expressions of K5, K8, K19 and K20 in males and K19 in females were maximised at R1. The K5, K20 and K75 gene levels in females peaked at R7. K75 and K8 expressions in males and females reached a maximum value at R25 and I17, respectively.4. The epithelial thickness of male and female crops reached their greatest levels at R1 and had the highest correlation with K19.5. These results emphasised the importance of keratinisation in crop milk formation, and different keratins probably play various roles during this period. The K19 was probably a marker for pigeon crop epithelium development. The sex of the parent pigeon affected keratin gene expression profiles.

[Effect of CKIP-1 on hepatocyte apoptosis in nonalcoholic fatty liver disease].

Objective: To explore the effect and underlying mechanism of casein kinase 2 interacting protein-1 (CKIP-1) on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD). Methods: Experimental study. An NAFLD cell model was established by inducing human hepatoma cell line, HepG2 cells, with oleic acid (OA). Flag-CKIP-1 expression vector and shRNA-CKIP-1 were transfected into HepG2 cells. Flow cytometry was used to detect the effect of CKIP-1 on the activity and apoptosis of NAFLD hepatocytes. The levels of apoptosis-related proteins were detected by Western blot. CKIP-1 knockout mice in C57BL/6 back-ground were fed with either standard or high-fat diet for 8 weeks. Apoptosis-related signal proteins in NAFLD hepatocytes were detected by immunohistochemistry. Results: After CKIP-1 was transfected into HepG2 cells, the degree of OA induced cell liposis was significantly reduced (P<0.05). Annexin V-FITC/PI flow cytometry showed that CKIP-1 reduced the apoptosis of steatotic hepatocytes. Overexpression of CKIP-1 could significantly inhibit the expression of caspase-3 and caspase-9 and increase the expression of Bcl-2/Bax (P<0.05). Knockdown of CKIP-1 could increase the expression of caspase-3 and caspase-9 (P<0.05). CKIP-1 knockout could further increase the expression of caspase-3 and caspase-9 in NAFLD mice (P<0.01,P<0.05), and further decrease the expression of Bcl-2/Bax (P<0.05). Conclusion: CKIP-1 inhibited the apoptosis of steatotic hepatocytes by up-regulating the expression of apoptosis inhibitor gene, Bcl-2/Bax, and affecting the proteases, caspase-3 and caspase-9.

[Effection of tear film stability on orthokeratology].

Orthokeratology (Ortho-K) is one of the effective methods to control the development of myopia in children and adolescents. The mechanical pressure of eyelids on the Ortho-K lens and the hydraulic effect of tears under the Ortho-K lens can alter the curvature or shape of the cornea, which can correct refractive error and control myopia development progress. The tear film is a thin layer of liquids evenly distributing in the conjunctival sac. Wearing an Ortho-K lens can decrease the tear film stability, which will influence the Ortho-K. In this article, the relevant domestic and overseas research results are summarized and analyzed, aiming to sort out and discuss the effection of tear film stability on the fitting, shaping, safety, and visual quality of the Ortho-K, as well as to provide suggestions for clinicians and researchers.

[Research updates on a role for retinal contrast in myopia control].

Animal research has established that signals derived from both contrast and defocus can influence refractive development, likely concurrently, so that overall refractive development reflects an integration of these primary visual signals. Important findings include the association of L/M opsin mutations with familial high myopia, axial hyperopia produced in response to form deprivation in moderate outdoor lighting levels, effective control of myopia by diffusion optics technology spectacle lenses designed to reduce retinal contrast, and all current defocus-based optical treatments which inadvertently reduce image contrast. In this review, clinical trial results of optical myopia treatment strategies that manipulate retinal contrast are considered in context of animal research outcomes. In conclusion, research suggests mild reductions in retinal contrast can slow myopia progression in children and may also have a role in defocus-based optical therapy.

Effects of phenylpyruvate on the growth performance and intestinal microbiota in broiler chicken.

1. The purpose of this study was to see how dietary supplementation with phenylpyruvate affected broiler growth, slaughter performance, gut health microbiota and immunity. This information can be used to develop alternative approaches to antibiotic replacement in modern poultry production and health.2. A total of 288, one-day-old broiler chickens were randomly assigned to one of four groups (six replicates each replicate has 12 chickens). A control basal diet (NC), basal diet plus antibiotic virginiamycin 15ppm (PC), basal diet plus phenylpyruvate 1 kg/t or 2 kg/t, respectively (LCP and HCP).3. Results showed that the birds in the PC group had higher ADFI during the first 21 d, and better FCR than the NC group. The HCP-fed group had a higher all-eviscerated ratio than the NC group and less abdominal fat than the birds fed LCP. The birds fed HCP had increased villus length and crypt depth in the ileum compared to the NC group.4. The bursa index was lower in the HCP group whereas the thymus index was lower in LCP and PC groups. In contrast, birds fed HCP has lower pro-inflammatory cytokine IL-1, as well as lower TLR4. Phenylpyruvate improved number in the Selenomonadaceae, genus Megamonas bacteroides spp., which are known for their beneficial effects on the maintenance of the cell surface structure, regulating aromatic amino acids and Clostridia jejuni-suppressive treatment respectively.5. It was concluded that phenylpyruvate can be utilised in feed to improve growth performance and positively modulate gut microbiota. However, this was less efficient than antibiotics in improving growth performance, although more efficient in improving productive performance and gut morphology. Moreover, a high dose of phenylpyruvate is more effective than a low dose.

Y-shaped airway self-expanding covered metallic stent removal via the interventional technique.

AIM: To review the removal of Y-shaped airway self-expanding covered metallic stents using the interventional technique under fluoroscopy. MATERIALS AND METHODS: The clinical data of 33 patients who underwent removal of Y-shaped airway self-expanding covered metallic stents from March 2011 to August 2019 were analysed retrospectively. RESULTS: A total of 35 Y-shaped stents were removed. The average indwelling duration of the tracheal stents was 101.7 ± 105.4 days. Four cases were removed via the conventional method (grasping the upper tip of the stent to collapse and adduct the proximal end of the stent), whereas 31 cases were removed using the reversal method (grasping the distal end of the stent to invert and strip out the stent). The duration of stent removal was 24.3 ± 12.4 minutes (median time, 20 minutes). CONCLUSION: The interventional radiology technique is a feasible, safe, and effective method for removing Y-shaped airway self-expanding covered metallic stents, and can be considered for use in the clinical setting.

Removal of covered metallic stents with a bullet head for bronchopleural fistula using a fluoroscopy-assisted interventional technique.

AIM: To investigate the feasibility and safety of a fluoroscopy-assisted interventional technique for removal of bullet-shaped self-expanding covered metallic stents from bronchopleural fistulas (BPFs). MATERIALS AND METHODS: Clinical data for 49 consecutive patients who underwent removal of bullet-shaped self-expanding covered metal stents from October 2010 to November 2019 were analysed retrospectively. Fifty-one stents were removed in all, including 29 large Y-shaped bullet stents, 10 small Y-shaped bullet stents, and 12 branched bullet-shaped stents. The average duration for which tracheal stents were in place was 99.4±8.5 days. RESULTS: Fifty-one stents were removed successfully, of which 49 were directly removed on the first attempt. The time required for stent removal ranged from 7-60 minutes (median time, 22 minutes). In eight cases, the stent was removed by the conventional method (i.e., grasping the upper tip of the stent to collapse and adduct the proximal end), and in 43 by the eversion method (i.e., grasping the distal end of the stent to invert and peel out). CONCLUSIONS: Interventional radiology is a simple, safe, and effective method to extract self-expanding covered metallic bullet-shaped stents, with no need for general anaesthesia and tracheal intubation. It has a short operation time, is well tolerated by patients, and is worthy of clinical application.

Gut microbiota of newborn piglets with intrauterine growth restriction have lower diversity and different taxonomic abundances.

AIM: Intrauterine growth retardation (IUGR) is a prevalent problem in mammals. The present study was conducted to unveil the alterations in intestinal microbiota in IUGR piglets. METHODS AND RESULTS: We identified the alterations of small intestinal microbiota in IUGR piglets on 7, 21 and 28 days of age using 16S rRNA sequencing. The results showed that IUGR piglets had a decreased alpha diversity of jejunum microbiota at 7 and 21 days of age; had lower abundances of Bacteroidetes and Bacteroides in the jejunum at 7, 21 and 28 days of age, Oscillibacter in the jejunum at 21 days of age, and Firmicutes in the ileum at 21 days of age; whereas they had higher abundances of Proteobacteria and Pasteurella in the ileum at 21 days of age and Escherichia-Shigella in the jejunum at 28 days of age. Correlation analysis showed that Bacteroides, Oscillibacter and Ruminococcaceae_UCG-002 compositions were positively associated with the body weight (BW) of IUGR piglets, nevertheless Proteobacteria and Escherichia-Shigella relative abundances were negatively correlated with the BW of IUGR piglets. Gene function prediction analysis indicated that microbiota-associated carbohydrate metabolism, lipid metabolism, glycan biosynthesis and metabolism, amino acid metabolism, and xenobiotics biodegradation and metabolism were downregulated in the IUGR piglets compared to control piglets. CONCLUSIONS: The present study profiled the intestinal microbiota of newborn piglets with IUGR and the newborn IUGR piglets have lower diversity and different taxonomic abundances. Alterations in the abundances of Bacteroidetes, Bacteroides, Proteobacteria Escherichia-Shigella and Pasteurella may be involved in nutrient digestion and absorption, as well as the potential mechanisms connecting to the growth and development of IUGR in mammals. SIGNIFICANCE AND IMPACT OF THE STUDY: The small intestinal microbiota were highly shaped in the IUGR piglets, which might further mediate the growth and development of IUGR piglets; and the gut microbiota could serve as a potential target for IUGR treatment.

Stages of pregnancy and weaning influence the gut microbiota diversity and function in sows.

AIMS: The gut microbiota is believed to play important roles in the health of pregnant mammals, including their nutrient metabolism, immune programming and metabolic regulation. However, until recently, the shifts in gut microbiota composition and faecal and blood metabolic activity during different stages of pregnancy had not been investigated. METHODS AND RESULTS: We investigated the shifts in backfat thickness, plasma and faecal metabolites and gut microbiota on days 30, 60, 90 and 110 of pregnancy and on day 21 after parturition (weaning) in sows. The backfat thickness of sows did not significantly differ among the different stages of pregnancy. The plasma concentrations of lipid metabolites, including triacylglycerol (TG), total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and calcium were reduced (P < 0·05) during pregnancy. In addition, the concentration of these metabolites, except TG, reached their maximum at the time of weaning. We also found that Tenericutes, Fibrobacteres and Cyanobacteria varied significantly according to the stages of pregnancy in sows (P < 0·05). Most of the genera, such as Clostridiales, Desulfovibrio, Mogibacteriaceae and Prevotella, increased (P < 0·05) with the progression of pregnancy and decreased (P < 0·05) at weaning. The alpha diversity values (i.e., Shannon diversity and observed species) of sow gut microbiota increased (P < 0·05) from pregnancy to weaning. Pregnancy stages also significantly influenced (P < 0·05) the community structure (beta diversity) of gut microbiota. The progression of pregnancy was associated with changes in lipid metabolism and several carbohydrate-degradation bacteria (i.e., Prevotella, Succinivibrio, Bacteroides and Parabacteroides). CONCLUSIONS: Although causal links between the measured parameters remain hypothetical, these findings suggest that the increased diversity and concentration of beneficial gut microbes are associated with the metabolism of pregnant sows. SIGNIFICANCE AND IMPACT OF THE STUDY: Manipulation of the sow gut microbiota composition may potentially influence metabolism and health during pregnancy.

Circ-ITCH regulates triple-negative breast cancer progression through the Wnt/ß-catenin pathway.

Recent studies indicate that circular RNA (circRNA) is involved in tumorigenesis, but its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, we characterized the role of circ-ITCH in TNBC and found that circ-ITCH was significantly down-regulated in TNBC tissues and cell lines and closely associated with poor prognosis. We therefore constructed the MDA-MB-231 and BT-549 TNBC cell lines stably expressing circ-ITCH by lentiviral vectors to determine its underlying mechanisms in TNBC progression. Most importantly, over-expression of circ-ITCH remarkably inhibited TNBC proliferation, invasion and metastasis both in vitro and in vivo. Mechanistically, we found that circ-ITCH acts as a sponge for miR-214 and miR-17 to increase expression of its ITCH linear isoform, thereby inactivating Wnt/ß-catenin signaling. Our combined results show for the first time that circ-ITCH is a tumor suppressor, a promising prognostic biomarker in TNBC and that its restoration could well be a successful strategy in TNBC.

[A machine learning model on orthokeratology lens fitting based on the data of optometry examination].

Objective: To get an orthokeratology lens fitting model according to the research of the optometry examination data, which can help to improve the work efficiency and increase the hitting rate of prescription. Methods: The relationship between the basic optometry examination data and the effective optometry prescription was evaluated. We got 1 467 sets of data, including 80%(1 173) for training and 20%(294) for testing. The trail results were used for the 20% testing sets, and 100% completed sets for verification. With the contrast of accuracy, we got the influencing variables and the fitting model. Logistic regression and linear regression analysis were applied to the training set for building a fitting model, and the receiver operating characteristic curve (ROC curve) was drawn to determine the optimal threshold of the logistic regression model (1.0).The trail results are used for the 20% testing sets, 100% completed sets for verification. With the contrast of accuracy (ACC), we get the influencing variables and the fitting model. Results: Kf-FK and Ks-SK were selected as dependent variables. Through analysis of Stepwise regression, we found the influencing variables of Kf-FK were Kf(P=0.01), E(mean) (P=0.027), and CYL(P<0.001), with FK=6.23+0.866kf-1.69 E(mean)+0.16CYL, and the precision rate was 81%(r(2)=0.95). The influencing variables of Ks-SK were Ks (P<0.001), CYL (P=0.00), and E(mean) (P<0.001), with SK=6.84+0.862ks-0.28E(mean)-1.3CYL, and the precision rate was 80%(r(2)=0.93). By selecting the logistic method and decision tree analysis for glasses design, the influencing variables were KS (P<0.001)and CYL (P<0.001). The logistic function was Design=-45.7+0.82Ks+6.027CYL, and the precision rate was 87%. Conclusions: The combination of AI and medical data can verify the expert experience and guide the optometrist to locate the prescription quickly and accurately. Try to break the traditional mode of fitting with wearing the orthokeratology lens shortly, and it is possible for us to position the prescription quickly through the calculation of a computer. (Chin J Ophthalmol, 2019, 55: 105-110).

Effect of selective serotonin reuptake inhibitors on bone mineral density: a systematic review and meta-analysis.

Our work is the first systematic meta-analysis to investigate the effect of selective serotonin reuptake inhibitor (SSRI) medication on bone mineral density. Through meta-analyzed 11 studies, our findings suggested that compared with nonusers, use of SSRIs was significantly associated with lumbar spine BMD reduction, particularly for old people. The use of selective serotonin reuptake inhibitors (SSRIs) has already been associated with bone mass loss. Their effects on bone mineral density (BMD) for the different bone sections have, however, thus been inconsistent. Here, we aim to assess the effects of SSRIs on BMD using a meta-analysis. We searched PubMed, Scopus, ISI Web of Knowledge, the Cochrane Library, and PsycINFO for all English-written studies investigating the effects of SSRIs on BMD and published before November 2017. BMD was compared between non-SSRI users and SSRI users using a random-effect model with standardized mean differences (SMD) and 95% confidence intervals (CIs). Furthermore, subgroup analyses were performed based on study design, age, and sex in order to find the origins of high heterogeneity. Eleven studies met the inclusion criteria and were used for the meta-analysis. Our study demonstrated that the use of SSRIs was significantly associated with lower BMD values (SMD - 0.40; 95% CI - 0.79 to 0.00; p = 0.05) and BMD Z-scores (SMD - 0.28; 95% CI - 0.50 to - 0.05; p = 0.02) of the lumbar spine, but not of the total hip and femoral neck. In addition, SSRI use was associated with a greater bone loss in older people. SSRI use is a risk factor of lower BMD of the lumbar spine, especially for older people. Future studies into the relationship between SSRI use and bone metabolism and bone mass need to be conducted with larger sample sizes for both men and women at different bone sites.

Changes in hepatic glucose and lipid metabolism-related parameters in domestic pigeon (Columba livia) during incubation and chick rearing.

This study aimed to evaluate the hepatic glucose and lipid metabolism-related parameters of adult male and female White King pigeons (Columba livia) during incubation and chick rearing. At day 4 (I4), 10 (I10) and 17 (I17) of incubation and day 1 (R1), 7 (R7), 15 (R15) and 25 (R25) of chick rearing, livers were sampled from six pigeons for each sex. Glycogen and fat contents, activities of glycolytic enzymes (hexokinase, HK; 6-phosphofructokinase, 6-PFK), and genes expressions of key enzymes involved in glycolysis (pyruvate kinase, PK; glucokinase, GK), gluconeogenesis (phosphoenolpyruvate carboxykinase cytosolic, PCK1; fructose-1,6-bisphosphatase, FBP1; glucose-6-phosphatase, G6Pase), fatty acid synthesis (fatty acid synthase, FAS; acetyl-CoA carboxylase, ACC) and fatty acid ß-oxidation (carnitine palmitoyltransferase 1, CPT1; acyl-CoA 1, ACO) were measured. In male and female pigeon livers, glycogen content and HK activity dramatically increased after I17 and after R1, respectively; expressions of FBP1 and G6Pase genes were maximized at R15; activity of 6-PFK and expressions of PK and CPT1 genes were highest at R7; fat content and expressions of FAS and ACC genes steeply increased from I10 to R1. In females, hepatic expressions of GK and PCK1 genes were greatest at R7 and I17, respectively; however, in males, both of them were maximized at R15. Hepatic expression of ACO gene was significantly enhanced at R1 compared to I17 and R7 in males, whereas it was notably up-regulated at I17 and R7 in females. Furthermore, expressions of PCK1, GK, FAS and ACC genes were in significant relation to fat content in the livers of female pigeons, while fat content in male pigeons was highly correlated with expression of PCK1, ACC, CPT1 and ACO genes. In conclusion, regulations of glucose and lipid metabolic processes were enhanced in parent pigeon livers from terminal phases of incubation to mid phase of chick rearing with sexual effects.

Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.

Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metabolism.

Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition.

The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1ß and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota-inflammasome-brain axis may offer novel therapeutic targets for psychiatric disorders.

Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with polynomial functions.

To infer the histories of population admixture, one important challenge with methods based on the admixture linkage disequilibrium (ALD) is to remove the effect of source LD (SLD), which is directly inherited from source populations. In previous methods, only the decay curve of weighted LD between pairs of sites whose genetic distance were larger than a certain starting distance was fitted by single or multiple exponential functions, for the inference of recent single- or multiple-wave admixture. However, the effect of SLD has not been well defined and no tool has been developed to estimate the effect of SLD on weighted LD decay. In this study, we defined the SLD in the formularized weighted LD statistic under the two-way admixture model and proposed a polynomial spectrum (p-spectrum) to study the weighted SLD and weighted LD. We also found that reference populations could be used to reduce the SLD in weighted LD statistics. We further developed a method, iMAAPs, to infer multiple-wave admixture by fitting ALD using a p-spectrum. We evaluated the performance of iMAAPs under various admixture models in simulated data and applied iMAAPs to the analysis of genome-wide single nucleotide polymorphism data from the Human Genome Diversity Project and the HapMap Project. We showed that iMAAPs is a considerable improvement over other current methods and further facilitates the inference of histories of complex population admixtures.

Analysis of genetic diversity of Leuciscus leuciscus baicalensis using novel microsatellite markers with cross-species transferability.

We used next-generation sequencing technology to characterize 19 genomic simple sequence repeat (SSR) markers and 11 expressed sequence tag (EST) SSR markers from Leuciscus leuciscus baicalensis, a small freshwater fish that is widely distributed in Xinjiang, China. Primers were used to test for polymorphisms in three L. leuciscus baicalensis populations in Xinjiang. There were 4-27 (average 11.3) alleles (NA), the expected heterozygosity (HE) was 0.36-0.94 (average 0.75 ± 0.14), the observed heterozygosity (HO) was 0.37-1.00 (average 0.68 ± 0.18), and the polymorphism information content (PIC) was 0.31-0.93 (average 0.71). The averages of HE and PIC for the EST-SSR markers were slightly lower than for the genomic SSR markers. Genetic analysis of the three populations showed similar results for PIC, HE, and NA. Amplifications were performed in nine other species; the top three transferability values were for Rutilus lacustris (80%), Leuciscus idus (76.7%), and Phoxinus ujmonensis (63.3%), with the following average values: PIC (0.56, 4.46, and 0.52); NA (0.40, 3.00, and 0.32); and HO (0.44, 2.74, and 0.22), respectively. L. leuciscus baicalensis is one of the most important commercial fish in Xinjiang, but in recent years, fishery resources have decreased sharply owing to water conservation projects, unreasonable utilization, and invasion by alien species. These novel SSR markers are appropriate for studies involving fingerprinting, gene flow, genetic diversity, population structure, and molecular-assisted breeding, and could contribute to the conservation of L. leuciscus baicalensis.