Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Variation of Inbreeding and Ancestry in the Remaining Two Isle Royale Wolves

Inbreeding, relatedness, and ancestry have traditionally been estimated with pedigree information, however, molecular genomic data can provide more detailed examination of these properties. For example, pedigree information provides estimation of the expected value of these measures but molecular genomic data can estimate the realized values of these measures in individuals. Here, we generate the theoretical distribution of inbreeding, relatedness, and ancestry for the individuals in the pedigree of the Isle Royale wolves, the first examination of such variation in a wild population with a known pedigree. We use the 38 autosomes of the dog genome and their estimated map lengths in our genomic analysis. Although it is known that the remaining wolves are highly inbred, closely related, and descend from only 3 ancestors, our analyses suggest that there is significant variation in the realized inbreeding and relatedness around pedigree expectations. For example, the expected inbreeding in a hypothetical offspring from the 2 remaining wolves is 0.438 but the realized 95% genomic confidence interval is from 0.311 to 0.565. For individual chromosomes, a substantial proportion of the whole chromosomes are completely identical by descent. This examination provides a background to use when analyzing molecular genomic data for individual levels of inbreeding, relatedness, and ancestry. The level of variation in these measures is a function of the time to the common ancestor(s), the number of chromosomes, and the rate of recombination. In the Isle Royale wolf population, the few generations to a common ancestor results in the high variance in genomic inbreeding.
Arabidopsis microRNA167 controls patterns of ARF6 and ARF8 expression, and regulates both female and male reproduction

In flowering plants, diploid sporophytic tissues in ovules and anthers support meiosis and subsequent haploid gametophyte development. These analogous reproductive functions suggest that common mechanisms may regulate ovule and anther development. Two Arabidopsis Auxin Response Factors, ARF6 and ARF8, regulate gynoecium and stamen development in immature flowers. Wild-type pollen grew poorly in arf6 arf8 gynoecia, correlating with ARF6 and ARF8 expression in style and transmitting tract. ARF6 and ARF8 transcripts are cleavage targets of the microRNA miR167, and overexpressing miR167 mimicked arf6 arf8 phenotypes. Mutations in the miR167 target sites of ARF6 or ARF8 caused ectopic expression of these genes in domains of both ovules and anthers where miR167 was normally present. As a result, ovule integuments had arrested growth, and anthers grew abnormally and failed to release pollen. Thus, miR167 is essential for correct patterning of gene expression, and for fertility of both ovules and anthers. The essential patterning function of miR167 contrasts with cases from animals in which miRNAs reinforce or maintain transcriptionally established gene expression patterns.
Relationship between soak time and number of enmeshed animals in experimentally lost gill nets

In order to determine the effects of ghost fishing by lost gill nets, the relationship was examined between soak time and number of enmeshed animals in experimentally lost gill nets by using diving observations. Two experimental gill nets were set at 13 m depth in Tateyama Bay, Chiba Prefecture, Japan for approximately 200 days. One gill net was deployed in a small trough surrounded by artificial reefs, and the other was deployed on an adjacent open sandy bed. Twelve species of crustaceans, six species of gastropods, and five species of bony fish were enmeshed in the experimental gill nets. The number of enmeshed animals in the artificial reef gill net was substantially larger than that in the sandy bed gill net. The number of enmeshed animals in the experimental gill nets increased rapidly within one month after deployment, and then declined gradually showing fluctuations caused by the decrease in newly enmeshed animals, and the drop off from gill nets caused by the decomposition of dead animals. The decrease in the number of enmeshed animals was expressed by logarithmic equations, and based on these equations, the duration of capture function for the lost gill nets was calculated to be 284–561 days in the artificial reef gill net and 200 days in the sandy bed gill net. The duration of capture function for the lost gill nets for non-commercial by-catch species such as small crustaceans and gastropods was longer than for commercial species such as Japanese spiny lobster and bony fish.
Numerical Investigation of the Surface Wave Formation in a Microwave Plasma Torch

The microwave plasma torch (MPT) is an attractive plasma source in both industry and scientific research because of its advantages in electrodeless operation ability, high energy efficiency, and flexibility under different operational conditions. However, relatively few numerical studies have been carried out for the MPT fed by a rectangular waveguide in two or even three dimensions. Therefore, this paper presents a 2-D, axisymmetric, and stationary fluid models to characterize the MPT, with an emphasis on the mechanism of the surface wave formation and the sustentation of the plasma column. Nine partial differential equations are included in this research, coupling microwave radiation, heat transfer, plasma bulk flow, and transport of different species with each other. The obtained results reveal how the traveling surface wave occurs and elucidate the consequent influence of the surface wave formation. Furthermore, this paper demonstrates the extension of the plasma column length and the propagation of the surface wave with an increase in the total plasma-absorbed microwave power. The dependence of the plasma column length on the plasma-absorbed microwave power is found to be motivated by the surface wave propagation. The limitations of the model and the difficulties in its numerical implementation are also discussed in the paper.
Quorum Sensing and Silencing in Vibrio parahaemolyticus

ABSTRACT The quorum regulatory cascade is poorly characterized in Vibrio parahaemolyticus, in part because swarming and virulence factors—the hallmarks of the organism—are repressed by this scheme of gene control, and quorum sensing seems to be silenced in many isolates. In these studies, we examine a swarming-proficient, virulent strain and identify an altered-function allele of the quorum regulator luxO that is demonstrated to produce a constitutively active mimic of LuxO∼P. We find that LuxO* affects the expression of three small regulatory RNAs (Qrrs) and the activity of a translational fusion in opaR, the output regulator. Tests for epistasis showed that luxO* is dominant over luxO and that opaR is dominant over luxO. Thus, information flow through the central elements of the V. parahaemolyticus quorum pathway is proven for the first time. Quorum-sensing output was explored using microarray profiling: the OpaR regulon encompasses ∼5.2% of the genome. OpaR represses the surface-sensing and type III secretion system 1 (T3SS1) regulons. One novel discovery is that OpaR strongly and oppositely regulates two type VI secretion systems (T6SS). New functional consequences of OpaR control were demonstrated: OpaR increases the cellular cyclic di-GMP (c-di-GMP) level, positively controls chitin-induced DNA competency, and profoundly blocks cytotoxicity toward host cells. In expanding the previously known quorum effects beyond the induction of the capsule and the repression of swarming to elucidate the global scope of genes in the OpaR regulon, this study yields many clues to distinguishing traits of this Vibrio species; it underscores the profoundly divergent survival strategies of the quorum On/Off phase variants.
Characterization of Hepatitis C Virus Particle Subpopulations Reveals Multiple Usage of the Scavenger Receptor BI for Entry Steps*

Background: SR-BI binds HCV E2 glycoprotein and lipoprotein components. Results: HCV entry exploits several SR-BI properties and different viral and cellular determinants present on the viral particles. Conclusion: SR-BI is a multifunctional entry factor essential for infectivity of HCV particles with different biophysical properties and host protein compositions. Significance: Studying HCV subpopulations reveals differential entry steps and receptor usage. Hepatitis C virus (HCV) particles assemble along the very low density lipoprotein pathway and are released from hepatocytes as entities varying in their degree of lipid and apolipoprotein (apo) association as well as buoyant densities. Little is known about the cell entry pathway of these different HCV particle subpopulations, which likely occurs by regulated spatiotemporal processes involving several cell surface molecules. One of these molecules is the scavenger receptor BI (SR-BI), a receptor for high density lipoprotein that can bind to the HCV glycoprotein E2. By studying the entry properties of infectious virus subpopulations differing in their buoyant densities, we show that these HCV particles utilize SR-BI in a manifold manner. First, SR-BI mediates primary attachment of HCV particles of intermediate density to cells. These initial interactions involve apolipoproteins, such as apolipoprotein E, present on the surface of HCV particles, but not the E2 glycoprotein, suggesting that lipoprotein components in the virion act as host-derived ligands for important entry factors such as SR-BI. Second, we found that in contrast to this initial attachment, SR-BI mediates entry of HCV particles independent of their buoyant density. This function of SR-BI does not depend on E2/SR-BI interaction but relies on the lipid transfer activity of SR-BI, probably by facilitating entry steps along with other HCV entry co-factors. Finally, our results underscore a third function of SR-BI governed by specific residues in hypervariable region 1 of E2 leading to enhanced cell entry and depending on SR-BI ability to bind to E2.
Effects of extracellular calcium on insulin‐like growth factor II in human bone cells

Extracellular calcium concentration is critically important for normal function of the body. Recently, reports have shown that cells derived from parathyroid glands contain an extracellular calcium receptor that is responsive to changes in extracellular calcium. Bone is also intimately involved in calcium homeostasis; therefore, we sought to test the hypothesis that extracellular calcium has direct effects on bone cells. Extracellular calcium was increased by the addition of varying concentrations of CaCl2 (0.4–2.0 mM) to the control medium. An increase in extracellular calcium increased cell proliferation, as assessed by 3H‐thymidine incorporation, in a number of cell types including normal human bone cells derived from vertebrae (HBV155) and a number of human osteosarcoma cell lines. The increase in cell proliferation by elevated CaCl2 was dose dependent, whereas MgCl2 was not effective at the doses tested (up to 2 mM added MgCl2). To test the hypothesis that the mitogenic activity of elevated extracellular calcium involved a growth factor, levels of insulin‐like growth factor II (IGF‐II) were measured in the conditioned medium of HBV155 cells by radioimmunoassay after removal of binding proteins by size exclusion chromatography. The effects of an increase in extracellular calcium by 1 mM were: 1) increased culture media levels of IGF‐II within 1 h of treatment, 2) the increase in IGF‐II levels reached a maximum after 8 h of treatment, and 3) IGF‐II levels were still elevated after 24 h of treatment. Furthermore, a blocking monoclonal antibody against IGF‐II abolished the increased cell proliferation in HBV155 cells following elevation of extracellular calcium. Taken together, these findings suggest that an increase in extracellular calcium results in an increase in IGF‐II which is required for the subsequent increase in cell proliferation.
Anti-inflammatory effects and mechanisms of vagal nerve stimulation combined with electroacupuncture in a rodent model of TNBS-induced colitis.

The purpose of this study was to determine the effects and mechanisms of vagal nerve stimulation (VNS) and additive effects of electroacupuncture (EA) on colonic inflammation in a rodent model of IBD. Chronic inflammation in rats was induced by intrarectal TNBS (2,4,6-trinitrobenzenesulfonic acid). The rats were then treated with sham ES (electrical stimulation), VNS, or VNS + EA for 3 wk. Inflammatory responses were assessed by disease activity index (DAI), macroscopic scores and histological scores of colonic tissues, plasma levels of TNFα, IL-1β, and IL-6, and myeloperoxidase (MPO) activity of colonic tissues. The autonomic function was assessed by the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. It was found that 1) the area under curve (AUC) of DAI was substantially decreased with VNS + EA and VNS, with VNS + EA being more effective than VNS (P < 0.001); 2) the macroscopic score was 6.43 ± 0.61 in the sham ES group and reduced to 1.86 ± 0.26 with VNS (P < 0.001) and 1.29 ± 0.18 with VNS + EA (P < 0.001); 3) the histological score was 4.05 ± 0.58 in the sham ES group and reduced to 1.93 ± 0.37 with VNS (P < 0.001) and 1.36 ± 0.20 with VNS + EA (P < 0.001); 4) the plasma levels of TNFα, IL-1β, IL-6, and MPO were all significantly decreased with VNS and VNS + EA compared with the sham ES group; and 5) autonomically, both VNS + EA and VNS substantially increased vagal activity and decreased sympathetic activity compared with sham EA (P < 0.001, P < 0.001, respectively). In conclusion, chronic VNS improves inflammation in TNBS-treated rats by inhibiting proinflammatory cytokines via the autonomic mechanism. Addition of noninvasive EA to VNS may enhance the anti-inflammatory effect of VNS.NEW & NOTEWORTHY This is the first study to address and compare the effects of vagal nerve stimulation (VNS), electrical acupuncture (EA) and VNS + EA on TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced colitis in rats. The proposed chronic VNS + EA, VNS, and EA were shown to decrease DAI and ameliorate macroscopic and microscopic damages in rats with TNBS-induced colitis via the autonomic pathway. The addition of EA to VNS provided a significant effect on the behavioral assessment of inflammation (DAI, CMDI, and histological score) but not on cytokines or mechanistic measurements, suggesting an overall systemic effect of EA.View this article's corresponding video summary at https://youtu.be/-rEz6HMkErM.
Ethanol increases extracellular dopamine concentration in the ventral striatum in C57BL/6 mice.

BACKGROUND Mesolimbic dopamine is thought to play a role in the reinforcing properties of ethanol, but ethanol-induced changes in extracellular dopamine in the ventral striatum have not been well characterized in mouse models. METHODS Two experiments were used to characterize the pharmacodynamic response of ethanol in the ventral striatum in C57BL/6 mice. The first experiment determined the effect of ethanol on ventral striatal dopamine in male and female mice after intraperitoneal injection of either 2.0 g/kg ethanol or saline. The second experiment was a replication in males, except that the mice were habituated to intraperitoneal injections before the dialysis experiment. RESULTS Distinct patterns of dopamine activity in response to ethanol were demonstrated in male and female C57BL/6 mice. A significant increase in dialysate dopamine relative to saline injection was observed in females but not in males. With habituation to intraperitoneal injection before the dialysis experiment, ethanol administration caused a significant dopamine response in males as well. A linear decline was observed in dialysate ethanol concentrations after the peak concentration was reached. Concurrent analysis of the time course of dopamine and ethanol content showed that the dopamine response declined significantly faster than the ethanol concentrations. CONCLUSIONS The C57BL/6 mouse strain is a justifiable model system for studying the mechanisms involved in ethanol regulation of mesolimbic dopamine activity. Habituation to intraperitoneal injection should be used in male C57BL/6 mice for experiments in which the dopamine response is measured after intraperitoneal injection of a drug. The dissociation between dopamine and ethanol may indicate an acute neural adaptation to ethanol-induced dopamine response in the ventral striatum after a single ethanol injection.
Spontaneous running activity in male rats: effect of age.

Alterations in the intensity and pattern of spontaneous running activity as rats increase in age from 7 wk to 1 yr was studied in male rats placed in exercise wheel cages. Daily running records were obtained on 27 rats for periods up to 12 mo, and 24-h activity recordings were made of selected runners to study the variation in activity during the day. The data indicate that for rats running over 2,940 revolutions (or 2 miles/day), the maximum intensity of running attained can be divided into a group of high achievers (approximately 8 miles/day) and moderate achievers (averaging 4.5 miles/day). For both groups, spontaneous running activity reached maximal rates after 4-5 wk. This maximal rate was sustained for 7-8 wk, then fell to levels approximately 60% of maximum for 4-5 mo, and then fell again to levels approximately 25% of maximum from 8 to 12 mo of age. The hourly pattern of running activity during the day was defined in rats of increasing age, who averaged 13,280, 6,662, 3,874, and 1,755 rev/day, corresponding to 9.0, 4.5, 2.6, and 1.2 miles/day, respectively. The overall patterns at each level indicated that the major running period occurred between 6:00 P.M. and 6:00 A.M., the greater activity of younger rats was paralleled by faster speeds and longer duration at each hour of the day, and the peak running activity for each group generally occurred between 7:00 and 9:00 P.M. In summary, there is a progressive loss in speed and duration of spontaneous running activity as male rats increase in age, with intensity of exercise falling below 2 miles/day after 7-8 mo of age.
Community-Acquired Pneumonia Requiring Admission to an Intensive Care Unit: A Descriptive Study

Severe community-acquired pneumonia (CAP) requiring admission to an intensive care unit (ICU) has been inadequately studied. We compared characteristics and outcomes of patients with CAP who were admitted to the ICU with those of patients managed on the ward. Of the 3675 patients hospitalized with CAP, 374 (10%) were admitted to the ICU. The main reason for ICU admission was respiratory failure requiring intubation and ventilation (n = 303, 81%), although this indication decreased with increasing age (p < 0.05 for trend). Most patients (62%) required mechanical ventilation for 3 days or less. The following factors were predictive of ICU admission on multivariable analysis: younger age, smoker, limitation of functional status, absence of cough or pleurisy, presence of chronic obstructive pulmonary disease, substance abuse, elevated serum creatinine, abnormal serum glucose concentration, and a respiratory rate of <16 or >24 breaths per minute. Patients with low Pneumonia Severity Index scores and low CURB-65 scores were admitted to the ICU based on clinical judgment that appeared to supersede objective scoring. Severe CAP requiring admission to the ICU is common, and the decision about which patients to admit often requires clinical judgment that in many cases appears at odds with various validated pneumonia severity scoring systems. Abbreviations: APACHE = Acute Physiology and Chronic Health Evaluation, BTS = British Thoracic Society rule, CAP = communityacquired pneumonia, COPD = chronic obstructive pulmonary disease, ICU = intensive care unit, PSI = Pneumonia Severity Index.
Biological effects induced by insulin‐like growth factor binding protein 3 (IGFBP‐3) in malignant melanoma

The insulin like growth factor (IGF) signaling pathway has been shown to contribute to melanoma progression, but little is known about the role of the IGF binding protein 3 (IGFBP‐3) in melanoma biology. The aim of the present study was to characterize expression, function and regulation of IGFBP‐3 in malignant melanomas and study its potential as a biomarker. The expression of IGFBP‐3 varied between different human melanoma cell lines and reintroduction of the protein in non‐expressing cells led to induction of apoptosis. Interestingly, in cell lines expressing endogenous IGFBP‐3, siRNA silencing of the protein led to a cell line‐dependent decrease in proliferation, but had no effect on apoptosis and invasion. Examination of patient material showed that IGFBP‐3 is unexpressed in benign nevi while a slight increase in protein expression was seen in primary and metastatic melanoma. However, expression of the protein was low and no correlation was found with circulating levels of IGFBP‐3 in serum, suggesting that IGFBP‐3 has limited potential as a predictive marker in malignant melanoma. We showed that promoter methylation of IGFBP‐3 occurred in both melanoma cell lines and patient material, implicating epigenetic silencing as a regulation mechanism. Furthermore, expression of the protein was shown to be regulated by the PI3‐kinase/AKT and MAPK/ERK1/2 pathways. In summary, our findings suggest that IGFBP‐3 can exert dual functional effects influencing both apoptosis and proliferation. Development of resistance to the antiproliferative effects of IGFBP‐3 may be an important step in progression of malignant melanomas.
Pretreatment prostate-specific antigen (PSA) velocity and doubling time are associated with outcome but neither improves prediction of outcome beyond pretreatment PSA alone in patients treated with radical prostatectomy.

PURPOSE Controversy exists as to whether current pretreatment prostate-specific antigen (PSA) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer. We assessed whether pretreatment PSA velocity (PSAV) or doubling time (PSADT) predicted outcome in men undergoing radical prostatectomy and whether any definition enhanced accuracy of an outcome prediction model. PATIENTS AND METHODS The cohort included 2,938 patients with two or more PSA values before radical prostatectomy. Biochemical recurrence (BCR) occurred in 384 patients, and metastases occurred in 63 patients. Median follow-up for patients without BCR was 2.1 years. We used univariate Cox proportional hazards regression to evaluate associations between published definitions of PSADT and PSAV with BCR and metastasis. Predictive accuracy was assessed using the concordance index. RESULTS On univariate analysis, two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis (P < .05). One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone, and four PSAV definitions improved prediction of metastasis. However, the improvements in predictive accuracy were small, associated with wide CIs, and markedly reduced if additional predictors of stage and grade were included alongside PSA. Modeling with random variables suggests that similar results would be expected by chance. CONCLUSION We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone.