Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Mycotoxins and Selenium Deficiency on Tissue-Engineered Cartilage

Objective: To investigate the effects of 3 mycotoxins, deoxynivalenol (DON), nivalenol (NIV) and T-2 toxin, in the presence and absence of selenium (Se) on the metabolism of tissue-engineered cartilage to mimic conditions found in Kashin-Beck disease (KBD) environments. Materials and Methods: Chondrocytes were seeded onto bone matrix gelatin (BMG) to construct engineered cartilage. The 3 toxins were added to the culture media for 3 weeks followed by immunhistochemical analyses of collagens type II and X, aggrecan, matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3), MMP inhibitors 1 and 3 (TIMP-1 and TIMP-3) and α2 macroglobulin (α2M). Results: Type II collagen was decreased while type X collagen was increased in response to DON, NIV and T-2 toxin. Aggrecan was reduced by all 3 mycotoxins. Compared with the control, the 3 toxins decreased the expression of α2M, TIMP-1 and TIMP-3, and increased the expression of MMP-1 and MMP-3. Se could partially inhibit the effects of DON, NIV and T-2 toxins. Conclusion: Under the low Se condition, the 3 mycotoxins produced procatabolic changes in cartilage resulting in the loss of aggrecan and type II collagen and promoted a hypertrophic phenotype of chondrocytes characterized by increasing type-X-collagen expression, enhancing the expression of MMPs, while weakening the TIMPs. Se could partially block the effects mentioned above. These results support the hypothesis that the combination of mycotoxin stress and Se deficiency would be the causative factors for KBD.
PATTERNS OF PATERNITY SKEW AMONG POLYANDROUS SOCIAL INSECTS: WHAT CAN THEY TELL US ABOUT THE POTENTIAL FOR SEXUAL SELECTION?

Monogamy results in high genetic relatedness among offspring and thus it is generally assumed to be favored by kin selection. Female multiple mating (polyandry) has nevertheless evolved several times in the social Hymenoptera (ants, bees, and wasps), and a substantial amount of work has been conducted to understand its costs and benefits. Relatedness and inclusive fitness benefits are, however, not only influenced by queen mating frequency but also by paternity skew, which is a quantitative measure of paternity biases among the offspring of polyandrous females. We performed a large‐scale phylogenetic analysis of paternity skew across polyandrous social Hymenoptera. We found a general and significant negative association between paternity frequency and paternity skew. High paternity skew, which increases relatedness among colony members and thus maximizes inclusive fitness gains, characterized species with low paternity frequency. However, species with highly polyandrous queens had low paternity skew, with paternity equalized among potential sires. Equal paternity shares among fathers are expected to maximize fitness benefits derived from genetic diversity among offspring. We discuss the potential for postcopulatory sexual selection to influence patterns of paternity in social insects, and suggest that sexual selection may have played a key, yet overlooked role in social evolution.
The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability.

A test-retest reliability study of the Structured Clinical Interview for DSM-III-R was conducted on 592 subjects in four patient and two nonpatient sites in this country as well as one patient site in Germany. For most of the major categories, kappa s for current and lifetime diagnoses in the patient samples were above . 60, with an overall weighted kappa of . 61 for current and . 68 for lifetime diagnoses. For the nonpatients, however, agreement was considerably lower, with a mean kappa of . 37 for current and . 51 for lifetime diagnoses. These values for the patient and nonpatient samples are roughly comparable to those obtained with other structured diagnostic instruments. Sources of diagnostic disagreement, such as inadequate training of interviewers, information variance, and low base rates for many disorders, are discussed.
Zinc Transport Complexes Contribute to the Homeostatic Maintenance of Secretory Pathway Function in Vertebrate Cells*

Zinc transporters play important roles in a wide range of biochemical processes. Here we report an important function of ZnT5/ZnT6 hetero-oligomeric complexes in the secretory pathway. The activity of human tissue-nonspecific alkaline phosphatase (ALP) expressed in ZnT5–ZnT7–/– cells was significantly reduced compared with that expressed in wild-type cells as in the case of endogenous chicken tissue-nonspecific ALP activity. The inactive human tissue-nonspecific ALP in ZnT5–ZnT7–/– cells was degraded by proteasome-mediated degradation without being trafficked to the plasma membrane. ZnT5–ZnT7–/– cells showed exacerbation of the unfolded protein response as did the wild-type cells cultured under a zinc-deficient condition, revealing that both complexes play a role in homeostatic maintenance of secretory pathway function. Furthermore, we showed that expression of ZnT5 mRNA was up-regulated by the endoplasmic reticulum stress in various cell lines. The up-regulation of the hZnT5 transcript was mediated by transcription factor XBP1 through the TGACGTGG sequence in the hZnT5 promoter, and this sequence was highly conserved in the ZnT5 genes of mouse and chicken. These results suggest that zinc transport into the secretory pathway is strictly regulated for the homeostatic maintenance of secretory pathway function in vertebrate cells.
FGF 1-mediated cardiomyocyte cell cycle reentry depends on the interaction of FGFR-1 and Fn 14

Fibroblast growth factors (FGFs) signal through FGF receptors (FGFRs) mediating a broad range of cellular functions during embryonic development, as well as disease and regeneration during adulthood. Thus, it is important to understand the underlying molecular mechanisms that modulate this system. Here, we show that FGFR-1 can interact with the TNF receptor superfamily member fibroblast growth factorinducible molecule 14 (Fn14) resulting in cardiomyocyte cell cycle reentry. FGF1-induced cell cycle reentry in neonatal cardiomyocytes could be blocked by Fn14 inhibition, while TWEAK-induced cell cycle activation was inhibited by blocking FGFR-1 signaling. In addition, costimulation experiments revealed a synergistic effect of FGF1 and TWEAK in regard to cardiomyocyte cell cycle induction via PI3K/Akt signaling. Overexpression of Fn14 with either FGFR-1 long [FGFR-1(L)] or FGFR-1 short [FGFR-1(S)] isoforms resulted after FGF1/TWEAK stimulation in cell cycle reentry of >40% adult cardiomyocytes. Finally, coimmunoprecipitation and proximity ligation assays indicated that endogenous FGFR-1 and Fn14 interact with each other in cardiomyocytes. This interaction was strongly enhanced in the presence of their corresponding ligands, FGF1 and TWEAK. Taken together, our data suggest that FGFR-1/Fn14 interaction may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control cardiomyocyte cell cycle reentry. —Novoyatleva, T. , Sajjad, A. , Pogoryelov, D. , Patra, C. , Schermuly, R. T. , Engel, F. B. FGF1-mediated cardiomyocyte cell cycle reentry depends on the interaction of FGFR-1 and Fn14. FASEB J. 28, 000–000 (2014). www.fasebj. org
Response Diversity Can Increase Ecological Resilience to Disturbance in Coral Reefs

Community-level resilience depends on the interaction between multiple populations that vary in individual responses to disturbance. For example, in tropical reefs, some corals can survive higher stress (resistance) while others exhibit faster recovery (engineering resilience) following disturbances such as thermal stress. While each type will negatively affect the other through competition, each might also benefit the other by reducing the potential for an additional competitor such as macroalgae to invade after a disturbance. To determine how community composition affects ecological resilience, we modeled coral-macroalgae interactions given either a resistant coral, a resilient coral, or both together. Having both coral types (i.e., response diversity) can lead to observable enhanced ecological resilience if (1) the resilient coral is not a superior competitor and (2) disturbance levels are high enough such that the resilient coral would collapse when considered alone. This enhanced resilience occurs through competitor-enabled rescue where each coral increases the potential for the other to recover from disturbance through external recruitment, such that both corals benefit from the presence of each other in terms of total cover and resilience. Therefore, conservation management aimed at protecting resilience under global change requires consideration of both diversity and connectivity between sites experiencing differential disturbance.
Dual Blockade of Interleukin-1β and Interleukin-17A Reduces Murine Arthritis Pathogenesis but Also Leads to Spontaneous Skin Infections in Nonhuman Primates

Despite the efficacy of biologics for treatment of rheumatoid arthritis (RA), many patients show inadequate responses and likely require neutralization of multiple mediators. Neutralization of both interleukin (IL)-1β and IL-17A with monoclonal antibodies showed greater efficacy than either agent alone in a mouse arthritis model with cooperative inhibition of key inflammatory factors, IL-6, granulocyte colony-stimulating factor (G-CSF), and CXC chemokine ligand (CXCL)1. Given the potential clinical benefit in RA, we generated a human dual variable domain antibody Ig, ABBV-615, capable of simultaneous binding and neutralization of IL-1β and IL-17A. ABBV-615 was characterized and evaluated in cynomolgus monkeys for pharmacokinetics and toxicity to enable clinical development. ABBV-615 exhibited affinities (KD) of 12 and 3 pM on human IL-1β and IL-17A, respectively, and potencies (IC50) of 3 and 58 pM, respectively, as well as excellent drug-like properties. ABBV-615 pharmacokinetics in cynomolgus monkeys was dose proportional from 20 to 100 mg/kg with a mean half-life of 16 days. However, a 13-week repeat-dose toxicity study in cynomolgus monkeys revealed time-dependent spontaneous infections exclusively in skin at all doses tested and not historically seen with single-agent anti–IL-1α/β or anti–IL-17A. Consistent with reduced resistance to skin infections, IL-1β– and IL-17A–stimulated human keratinocytes demonstrate cooperative or compensatory production of key antibacterial and inflammatory mediators such as lipocalin-2, G-CSF, CXCL1, IL-8, tumor necrosis factor, and IL-6, which aid in defense against skin bacterial infections. These results illustrate the skin-specific antimicrobial mechanisms of IL-1β and IL-17A and highlight the importance of understanding unique combinatorial effects of biologic agents.
A proteomic determination of cold adaptation in the Antarctic archaeon, Methanococcoides burtonii

A global view of the biology of the cold‐adapted archaeon Methanococcoides burtonii was achieved using proteomics. Proteins specific to growth at 4°C versus Topt (23°C) were identified by mass spectrometry using the draft genome sequence of M. burtonii. mRNA levels were determined for all genes identified by proteomics, and specific enzyme assays confirmed the protein expression results. Key aspects of cold adaptation related to transcription, protein folding and metabolism, including specific roles for RNA polymerase subunit E, a response regulator and peptidyl prolyl cis/trans isomerase. Heat shock protein DnaK was expressed during growth at Topt, indicating that growth at ‘optimal’ temperatures was stressful for this cold‐adapted organism. Expression of trimethylamine methyltransferase involves contiguous translation of two open reading frames, which is likely to result from incorporation of pyrrolysine at an amber stop codon. Thermal regulation in M. burtonii is achieved through complex gene expression events involving gene clusters and operons, through to protein modifications.
Steroid-avoidance immunosuppression regimen in live-donor renal allotransplant recipients: a prospective, randomized, controlled study.

OBJECTIVES Steroids have occupied a major role in renal transplantation for more than 4 decades. However, chronic use of steroids is associated with numerous comorbidities. We sought to elucidate the safety and efficacy of a steroid-free immunosuppression regimen in live-donor renal transplant recipients. PATIENTS AND METHODS One hundred patients were randomized to receive tacrolimus, mycophenolate mofetil, basiliximab induction, and steroids only for 3 days (experimental group, n=50 patients) or tacrolimus, mycophenolate mofetil, basiliximab induction, and steroid maintenance (control group, n=50 patients,). The median follow-up was 12 months. RESULTS Patient and graft survival rates were 100% in both groups. The rate of biopsy-proven acute rejection was 16% in both groups. For patients in the control group, the mean serum creatinine level was 111.22 micromol /L compared with 110.39 micromol/L in patients in the experimental group. Posttransplant hypertension was encountered in 4% of the patients in the experimental group compared with 24% of the patients in the control group (P = .0009). Posttransplant diabetes mellitus was detected in 4% of the patients in the experimental group compared with 16% of the patients in the control group (P = .037). Posttransplant weight gain was reported in 6% of the patients in the experimental group compared with 15% of the patients in the control group (P = .001). The chronic allograft damage indexes of biopsy specimens at 1-year follow-up were comparable in both groups (2.48 vs 2.28, respectively) (P = .16). CONCLUSIONS In living-donor renal transplant recipients with low immunologic risk, steroid avoidance (using basiliximab induction, tacrolimus, mycophenolate mofetil maintenance, and 3 days' steroid treatment) is feasible, safe, and carries with it fewer morbidities compared with the same immunosuppressive protocol with steroid maintenance. Longer follow-ups are required to prove the safety of this regimen.
Cocaine Inhibits Production of Murine Hepatitis Virus by Peritoneal Macrophages In Vitro

Abstract Our previous studies have demonstrated a number of effects of cocaine on macrophage (MØ) functions. The present studies were initiated to ascertain the effects of cocaine on virus production in vitro. C57BL/6 mice were injected intraperitoneally with thioglycollate broth, and the peritoneal MØ collected 4 days later were cultured in 96-well microtiter plates as continuous monolayers. Various concentrations of cocaine were incubated with MØ for up to 5 days. Mouse hepatitis virus (MHV) was added to these cultures, which was followed by a methyl cellulose overlay. Cocaine caused a dose-dependent inhibition of viral plaques after 48 hr of incubation. The inhibitory activity was transferable to fresh cultures of MØ, inhibiting both plaque size and number. Specific polyclonal antibodies to α + β-interferon but not tumor necrosis factor or transforming growth factor-β partially reversed the inhibition of both plaque size and plaque number. It appears that MHV induced interferon in cultured MØ, an effect that was enhanced by cocaine. Since cocaine has been reported to interfere with calcium mobilization, studies were done using ionomycin, a calcium ionophore, in order to reverse possible effects on intracellular calcium that could affect virus production. The presence of ionomycin completely reversed the inhibition of virus production by cocaine. The antiviral effects of cocaine appear to be caused by modulation of intracellular calcium and, to a lesser extent, by the enhancement of interferon production.
Antisense Ki-67 cDNA Transfection Reverses the Tumorigenicity and Induces Apoptosis in Human Breast Cancer Cells

Effects of antisense Ki-67 cDNA transfection on breast cancer cells were investigated in this study. Transfection of antisense Ki-67 cDNA resulted in a 70%–80% reduction in proliferation of MDA-MB-435s, cells which highly expressed Ki-67 mRNA and protein. Transwell assay showed that mobility and invasion capability was dramatically inhibited by 50%–60%, and cell cycle analysis displayed a higher proportion in G2/M and G0/G1 phases accompanied by remarkably increased ratio of apoptotic cells. Our results suggested that antisense Ki-67 cDNA vector treatment might be an important potential option in the anticancer therapy.
Milk Products, Insulin Resistance Syndrome and Type 2 Diabetes

A growing body of evidence suggests an inverse relationship between calcium and vitamin D status and dairy food intake and the development of the insulin resistance syndrome (IRS) and type 2 diabetes mellitus (t2DM). Observational studies show a consistent inverse association between dairy intake and the prevalence of IRS and t2DM. In a systematic review of the observational evidence, the odds for developing the IRS was 0.71 (95% CI, 0,57–0.89) for the highest dairy intake (3–4 servings/d) vs. the lowest intake (0.9–1.7 servings/d). Few interventional studies have been conducted to evaluate the effects of dairy food intake on the management of prevention of IRS or t2DM. Intervention studies that have examined the independent effects of dairy intake on specific metabolic components of the IRS including blood pressure and obesigenic parameters have shown favorable effects that support the observational findings albeit the results have been less consistent. Many metabolic and dietary factors appear to influence the degree to which dairy affects IRS metabolic parameters including calcium and vitamin D intake status, BMI, ethnicity and age. Overall, the intake of low-fat dairy products is a feature of a healthy dietary pattern which has been shown to contribute to a significant extent to the prevention of IRS.
Impact of plasma lipids and time on memory performance in healthy elderly without dementia

Objective: To examine the association of plasma lipid levels to changes in cognitive function in elderly subjects without dementia. Methods: The authors examined changes in performance in tests of memory, visuospatial/cognitive, and language abilities in 1,147 elderly individuals without dementia or cognitive impairment at baseline followed for 7 years using generalized estimating equations. Results: Performance in all cognitive domains declined significantly over time, while there was no association between levels of any plasma lipid or lipid lowering treatment and memory, cognitive/visuospatial, or language performance at any interval. Higher age at baseline was related to lower scores in all three domains at each interval, while higher education and white ethnicity were associated with higher scores in all domains. Analyses relating plasma lipids to performance in color trails tests using proportional hazards regression showed no association. In subsequent analyses excluding subjects with incident dementia, memory performance declined over time, while cognitive/visuospatial and language performance did not. Higher plasma high density lipoprotein and total cholesterol were associated with higher scores in language performance at baseline; this domain declined faster among individuals with higher total cholesterol, but this result was not significant after taking multiple comparisons into account. Plasma triglycerides, low density lipoprotein, or treatment with lipid lowering agents were not associated with changes in cognitive performance. Conclusions: Plasma lipid levels or treatment with lipid lowering agents in the elderly were not associated with changes in cognitive function.
Assessment of the Impact of Fiscal Policy on the Current Account – the Twin Deficit Hypothesis in the Case of Macedonian Economy

For a small open economy with fixed exchange rate regime, the twin deficit hypothesis is always an interesting and relevant research topic. The aim of this research is to evaluate the effects of the government budget shocks on the current account movement in the case of the Macedonian economy, hoping to shed light on the influence of the fiscal policy on the external position of the economy, as well as to provide useful guidance for policy makers about the sensitivity of the current account balance to changes in the primary budget balance. By using a VAR model on quarterly data for the period from 1998 to 2013, this paper points to a positive relationship between the two balances, but the empirical results also indicate that connection is only contemporaneous, implying that fiscal policy stance does not cause long lasting changes in the balance of payments position of the Macedonian economy. However, our results do not undemand the need for fiscal cautiousness, especially in an economy with a fixed exchange rate regime.
Demand as Frequency Controlled Reserve

Relying on generation side alone is deemed insufficient to fulfill the system balancing needs for future Danish power system, where a 50% wind penetration is outlined by the government for year 2025. This paper investigates use of the electricity demand as frequency controlled reserve (DFR), which has a high potential and can provide many advantages. Firstly, the background of the research is reviewed, including conventional power system reserves and the demand side potentials. Subsequently, the control logics and corresponding design considerations for the DFR technology have been developed and analyzed, based on which simulation models have been built using the DIgSILENT Power Factory. The simulation studies of different scenarios confirm that the DFR can provide reliable performance of frequency control. Furthermore, relevant issues regarding implementing DFR in reality have been discussed.
Lymphocyte subpopulations in pyogranulomas of caseous lymphadenitis

Pyogranulomas of ovine caseous lymphadenitis (CLA) are encapsulated lesions resulting from infections with Corynebacterium pseudotuberculosis, a bacterial pathogen able to grow within macrophages. Immunohistology of CLA lesions showed a band of lymphocytes lining the inside of the collagen capsule in intimate contact with necrotic tissue, the intracapsular lymphocytes being organized into three layers. The innermost layer, immediately adjacent to the central necrotic tissue consisted of a narrow band of MHC class II staining macrophages. Cells staining for CD4. CD8 and γδ T cell markers were unevenly distributed throughout the lymphoid layer, tending to be more numerous immediately external to the macrophage layer. The intracapsular lymphoid tissue contained a high proportion of CD8+ lymphocytes (CD4:CD8, 1.5:1) and of γδ lymphocytes (CD4:CD8:γδ, 1:0.7:0.8). External to the T cell‐rich zone and adjacent to the surrounding collagen capsule was a dense band of cells, a proportion of which stained atypically for CD45R and were tentatively identified as B cells. CDS+ and γδ+ T cells showed similar distributions and their relative abundance, compared with CD4+ T cells, was a distinguishing feature of the CLA lesion. Staining for factor VIII‐related antigen clearly showed endothelial venules throughout the intracapsular lymphoid tissue. The presence of endolhelial vcnules and the organized architecture of the lymphoid tissue teleologically argues that lymphocytes are continually recruited into chronic CLA lesions and play an important role in the ongoing disease process.