Resistenzen bei Bakterienisolaten aus der Nase von Aufzuchtkälbern in Milchviehbetrieben

Fifty-six E. coli, 37 P. multocida und 8 M. haemolytica were isolated from 157 nasal swabs taken from calves in 52 dairy herds. The antibiotic susceptibility of the organisms was determined by measurement of the minimal inhibitory concentrations. Of the 56 E. coli isolates, 55.3% exhibited resistance to tetracyclines, 55.3% to sulfonamides, 39.3% to beta-lactams, 30.3% to aminoglycosides, 8.9% to fluorochinolones and 3.5% to 3rd generation cephalosporins. The 3rd generation cephalosporin- resistant isolates contained the extended spectrum-beta-lactamase gene blaCTX-M-14 and came from 2 farms where the milk of cows under antimicrobial treatment was fed to the calves and mastitis was treated with cefquinome as first line therapy. Of the 37 P. multocida isolates, 48.6% exhibited resistance to tetracyclines, 16.2% to beta-lactams, and 5.4% each to macrolides, aminoglycosides and sulfonamides. The 8 M. haemolytica isolates showed no resistances against the tested antibiotics

Associations of antimicrobial use with antimicrobial susceptibility at the calf level in bacteria isolated from the respiratory and digestive tracts of veal calves before slaughter.

OBJECTIVES Antimicrobial drugs are frequently administered in veal calves, but investigations on associations with antimicrobial susceptibility of bacteria are scarce and convey partly contradictory findings. The aim of this study was to investigate associations of antimicrobial use (AMU) during the fattening period with antimicrobial susceptibility shortly before slaughter. METHODS Detailed treatment data of 1905 veal calves from 38 farms were collected prospectively during monthly farm visits for 1 year (n = 1864 treatments, n = 535 visits); 1582 Escherichia coli, 1059 Pasteurella multocida and 315 Mannheimia haemolytica were isolated from rectal and nasopharyngeal swabs collected before slaughter and subjected to antimicrobial susceptibility testing by microdilution. Associations of antimicrobial treatments with resistant isolates were investigated at the calf level. RESULTS Associations of AMU with antimicrobial resistance were observed using generalized linear models. For E. coli, the odds of being resistant were increased with increased AMU (OR 1.36 when number of treatments >1, P = 0.066). Use of tetracyclines was associated with resistance to tetracycline (OR 1.86, P < 0.001) and use of penicillins was associated with resistance to ampicillin (OR 1.66, P = 0.014). No significant associations were observed for P. multocida (use of aminoglycosides: OR 3.66 for resistance to spectinomycin, P = 0.074). For M. haemolytica, the odds of being resistant were increased with increased AMU (OR 4.63, P < 0.001), and use of tetracyclines was associated with resistance to tetracycline (OR 6.49, P < 0.001). CONCLUSIONS Occurrence of resistant bacteria shortly before slaughter was associated with AMU in veal calves. Prudent and appropriate use may contribute to limit the selection of resistant bacteria on veal farms

Mutant <i>CTNNB1</i> and histological heterogeneity define metabolic subtypes of hepatoblastoma.

Hepatoblastoma is the most common malignant pediatric liver cancer. Histological evaluation of tumor biopsies is used to distinguish among the different subtypes of hepatoblastoma, with fetal and embryonal representing the two main epithelial components. With frequent &lt;i&gt;CTNNB1&lt;/i&gt; mutations, hepatoblastoma is a Wnt/β-catenin-driven malignancy. Considering that Wnt activation has been associated with tumor metabolic reprogramming, we characterized the metabolic profile of cells from hepatoblastoma and compared it to cells from hepatocellular carcinoma. First, we demonstrated that glucose transporter &lt;i&gt;GLUT3&lt;/i&gt; is a direct TCF4/β-catenin target gene. RNA sequencing enabled to identify molecular and metabolic features specific to hepatoblastoma and revealed that several glycolytic enzymes are overexpressed in embryonal-like compared to fetal-like tumor cells. This led us to implement successfully three biomarkers to distinguish embryonal from fetal components by immunohistochemistry from a large panel of human hepatoblastoma samples. Functional analyses demonstrated that embryonal-like hepatoblastoma cells are highly glycolytic and sensitive to hexokinase-1 silencing. Altogether, our findings reveal a new, metabolic classification of human hepatoblastoma, with potential future implications for patients' diagnosis and treatment

Field tests of performance and their relationship to age and anthropometric parameters in adolescent handball players

Handball performance is influenced by age, anthropometric characteristics, technical skills, tactical understanding, and physical abilities. The aims of this study were (i) to determine differences in anthropometric characteristics and physical performance between adolescent handball players across age categories, and (ii) to determine which anthropometric and maturity variables have the greatest relative importance in fitness for this sport. Seventy-nine male handball players drawn from a team in the elite Tunisian Handball league [U18 ( = 10); U17 ( = 12); U16 ( = 17); U15 ( = 18); and U14 ( = 22)] volunteered for the investigation. Assessments included sprint performances; change in direction tests (T-half test and Illinois modified test); jumping tests (squat jump; counter movement jump; countermovement jump with aimed arms; five-jump test); medicine ball throwing; handgrip force; back extensor force and selected anthropometric measurements. The individual's age category affected all measurements, with U17 and U18 players showing larger body measurements and significantly better absolute results on all physical tests than U14, U15 and U16 contestants. Scores for the majority of physical performance tests were closely inter-correlated. We conclude that U17 and U18 players show significantly better absolute results than the younger players on all physical tests. Multiple linear regressions, using block-wise entry, indicate that age is the strongest predictor of jump and sprint performances. Several anthropometric characteristics, including body mass, standing height and lower limb length were closely correlated with performance test scores, but after allowing for age only body mass added to the prediction of jumping ability

Distinct Regulation of Host Responses by ERK and JNK MAP Kinases in Swine Macrophages Infected with Pandemic (H1N1) 2009 Influenza Virus

Swine influenza is an acute respiratory disease in pigs caused by swine influenza virus (SIV). Highly virulent SIV strains cause mortality of up to 10%. Importantly, pigs have long been considered “mixing vessels” that generate novel influenza viruses with pandemic potential, a constant threat to public health. Since its emergence in 2009 and subsequent pandemic spread, the pandemic (H1N1) 2009 (H1N1pdm) has been detected in pig farms, creating the risk of generating new reassortants and their possible infection of humans. Pathogenesis in SIV or H1N1pdm-infected pigs remains poorly characterized. Proinflammatory and antiviral cytokine responses are considered correlated with the intensity of clinical signs, and swine macrophages are found to be indispensible in effective clearance of SIV from pig lungs. In this study, we report a unique pattern of cytokine responses in swine macrophages infected with H1N1pdm. The roles of mitogen-activated protein (MAP) kinases in the regulation of the host responses were examined. We found that proinflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were significantly induced and their induction was ERK1/2-dependent. IFN-β and IFN-inducible antiviral Mx and 2′5′-OAS were sharply induced, but the inductions were effectively abolished when ERK1/2 was inhibited. Induction of CCL5 (RANTES) was completely inhibited by inhibitors of ERK1/2 and JNK1/2, which appeared also to regulate FasL and TNF-α, critical for apoptosis in pig macrophages. We found that NFκB was activated in H1N1pdm-infected cells, but the activation was suppressed when ERK1/2 was inhibited, indicating there is cross-talk between MAP kinase and NFκB responses in pig macrophages. Our data suggest that MAP kinase may activate NFκB through the induction of RIG-1, which leads to the induction of IFN-β in swine macrophages. Understanding host responses and their underlying mechanisms may help identify venues for effective control of SIV and assist in prevention of future influenza pandemics

Disruption of TLR3 Signaling Due to Cleavage of TRIF by the Hepatitis A Virus Protease-Polymerase Processing Intermediate, 3CD

Toll-like receptor 3 (TLR3) and cytosolic RIG-I-like helicases (RIG-I and MDA5) sense viral RNAs and activate innate immune signaling pathways that induce expression of interferon (IFN) through specific adaptor proteins, TIR domain-containing adaptor inducing interferon-β (TRIF), and mitochondrial antiviral signaling protein (MAVS), respectively. Previously, we demonstrated that hepatitis A virus (HAV), a unique hepatotropic human picornavirus, disrupts RIG-I/MDA5 signaling by targeting MAVS for cleavage by 3ABC, a precursor of the sole HAV protease, 3Cpro, that is derived by auto-processing of the P3 (3ABCD) segment of the viral polyprotein. Here, we show that HAV also disrupts TLR3 signaling, inhibiting poly(I:C)-stimulated dimerization of IFN regulatory factor 3 (IRF-3), IRF-3 translocation to the nucleus, and IFN-β promoter activation, by targeting TRIF for degradation by a distinct 3ABCD processing intermediate, the 3CD protease-polymerase precursor. TRIF is proteolytically cleaved by 3CD, but not by the mature 3Cpro protease or the 3ABC precursor that degrades MAVS. 3CD-mediated degradation of TRIF depends on both the cysteine protease activity of 3Cpro and downstream 3Dpol sequence, but not 3Dpol polymerase activity. Cleavage occurs at two non-canonical 3Cpro recognition sequences in TRIF, and involves a hierarchical process in which primary cleavage at Gln-554 is a prerequisite for scission at Gln-190. The results of mutational studies indicate that 3Dpol sequence modulates the substrate specificity of the upstream 3Cpro protease when fused to it in cis in 3CD, allowing 3CD to target cleavage sites not normally recognized by 3Cpro. HAV thus disrupts both RIG-I/MDA5 and TLR3 signaling pathways through cleavage of essential adaptor proteins by two distinct protease precursors derived from the common 3ABCD polyprotein processing intermediate

Genes Involved in the Balance between Neuronal Survival and Death during Inflammation

Glucocorticoids are potent regulators of the innate immune response, and alteration in this inhibitory feedback has detrimental consequences for the neural tissue. This study profiled and investigated functionally candidate genes mediating this switch between cell survival and death during an acute inflammatory reaction subsequent to the absence of glucocorticoid signaling. Oligonucleotide microarray analysis revealed that following lipopolysaccharide (LPS) intracerebral administration at striatum level, more modulated genes presented transcription impairment than exacerbation upon glucocorticoid receptor blockage. Among impaired genes we identified ceruloplasmin (Cp), which plays a key role in iron metabolism and is implicated in a neurodegenative disease. Microglial and endothelial induction of Cp is a natural neuroprotective mechanism during inflammation, because Cp-deficient mice exhibited increased iron accumulation and demyelination when exposed to LPS and neurovascular reactivity to pneumococcal meningitis. This study has identified genes that can play a critical role in programming the innate immune response, helping to clarify the mechanisms leading to protection or damage during inflammatory conditions in the CNS

Activated K-ras and INK4a/Arf Deficiency Cooperate During the Development of Pancreatic Cancer by Activation of Notch and NF-κB Signaling Pathways

BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States, suggesting that novel strategies for the prevention and treatment of PDAC are urgently needed. K-ras mutations are observed in >90% of pancreatic cancer, suggesting its role in the initiation and early developmental stages of PDAC. In order to gain mechanistic insight as to the role of mutated K-ras, several mouse models have been developed by targeting a conditionally mutated K-ras(G12D) for recapitulating PDAC. A significant co-operativity has been shown in tumor development and metastasis in a compound mouse model with activated K-ras and Ink4a/Arf deficiency. However, the molecular mechanism(s) by which K-ras and Ink4a/Arf deficiency contribute to PDAC has not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS:To assess the molecular mechanism(s) that are involved in the development of PDAC in the compound transgenic mice with activated K-ras and Ink4a/Arf deficiency, we used multiple methods, such as Real-time RT-PCR, western blotting assay, immunohistochemistry, MTT assay, invasion, EMSA and ELISA. We found that the deletion of Ink4a/Arf in K-ras(G12D) expressing mice leads to PDAC, which is in part mediated through the activation of Notch and NF-κB signaling pathways. Moreover, we found down-regulation of miR-200 family, which could also play important roles in tumor development and progression of PDAC in the compound transgenic mice. CONCLUSIONS/SIGNIFICANCE:Our results suggest that the activation of Notch and NF-κB together with the loss of miR-200 family is mechanistically linked with the development and progression of PDAC in the compound K-ras(G12D) and Ink4a/Arf deficient transgenic mice

Using Satellite Tracking to Optimize Protection of Long-Lived Marine Species: Olive Ridley Sea Turtle Conservation in Central Africa

Tractable conservation measures for long-lived species require the intersection between protection of biologically relevant life history stages and a socioeconomically feasible setting. To protect breeding adults, we require knowledge of animal movements, how movement relates to political boundaries, and our confidence in spatial analyses of movement. We used satellite tracking and a switching state-space model to determine the internesting movements of olive ridley sea turtles (Lepidochelys olivacea) (n = 18) in Central Africa during two breeding seasons (2007-08, 2008-09). These movements were analyzed in relation to current park boundaries and a proposed transboundary park between Gabon and the Republic of Congo, both created to reduce unintentional bycatch of sea turtles in marine fisheries. We additionally determined confidence intervals surrounding home range calculations. Turtles remained largely within a 30 km radius from the original nesting site before departing for distant foraging grounds. Only 44.6 percent of high-density areas were found within the current park but the proposed transboundary park would incorporate 97.6 percent of high-density areas. Though tagged individuals originated in Gabon, turtles were found in Congolese waters during greater than half of the internesting period (53.7 percent), highlighting the need for international cooperation and offering scientific support for a proposed transboundary park. This is the first comprehensive study on the internesting movements of solitary nesting olive ridley sea turtles, and it suggests the opportunity for tractable conservation measures for female nesting olive ridleys at this and other solitary nesting sites around the world. We draw from our results a framework for cost-effective protection of long-lived species using satellite telemetry as a primary tool