Structural basis for dual roles of Aar2p in U5 snRNP assembly

Yeast U5 small nuclear ribonucleoprotein particle (snRNP) is assembled via a cytoplasmic precursor that contains the U5-specific Prp8 protein but lacks the U5-specific Brr2 helicase. Instead, pre-U5 snRNP includes the Aar2 protein not found in mature U5 snRNP or spliceosomes. Aar2p and Brr2p bind competitively to a C-terminal region of Prp8p that comprises consecutive RNase H-like and Jab1/MPN-like domains. To elucidate the molecular basis for this competition, we determined the crystal structure of Aar2p in complex with the Prp8p RNase H and Jab1/MPN domains. Aar2p binds on one side of the RNase H domain and extends its C terminus to the other side, where the Jab1/MPN domain is docked onto a composite Aar2p–RNase H platform. Known Brr2p interaction sites of the Jab1/MPN domain remain available, suggesting that Aar2p-mediated compaction of the Prp8p domains sterically interferes with Brr2p binding. Moreover, Aar2p occupies known RNA-binding sites of the RNase H domain, and Aar2p interferes with binding of U4/U6 di-snRNA to the Prp8p C-terminal region. Structural and functional analyses of phospho-mimetic mutations reveal how phosphorylation reduces affinity of Aar2p for Prp8p and allows Brr2p and U4/U6 binding. Our results show how Aar2p regulates both protein and RNA binding to Prp8p during U5 snRNP assembly

"Last-Mile" preparation for a potential disaster

Extreme natural events, like e.g. tsunamis or earthquakes, regularly lead to catastrophes with dramatic consequences. In recent years natural disasters caused hundreds of thousands of deaths, destruction of infrastructure, disruption of economic activity and loss of billions of dollars worth of property and thus revealed considerable deficits hindering their effective management: Needs for stakeholders, decision-makers as well as for persons concerned include systematic risk identification and evaluation, a way to assess countermeasures, awareness raising and decision support systems to be employed before, during and after crisis situations. The overall goal of this study focuses on interdisciplinary integration of various scientific disciplines to contribute to a tsunami early warning information system. In comparison to most studies our focus is on high-end geometric and thematic analysis to meet the requirements of small-scale, heterogeneous and complex coastal urban systems. Data, methods and results from engineering, remote sensing and social sciences are interlinked and provide comprehensive information for disaster risk assessment, management and reduction. In detail, we combine inundation modeling, urban morphology analysis, population assessment, socio-economic analysis of the population and evacuation modeling. The interdisciplinary results eventually lead to recommendations for mitigation strategies in the fields of spatial planning or coping capacity

Smartamine M Supplementation Reduces Inflammation but Does Not Affect Performance in Receiving Beef Heifers

Objective: This study was conducted to evaluate the ability of supplemental methionine to improve health, inflammation status, and performance of receiving cattle. Study Description: A group of 384 crossbred heifers (initial weight 489 lb) of Tennessee origin were used in a 45-day receiving trial with limit-feeding to evaluate the effects of supplemental methionine (Smartamine M; Adisseo, Alpharetta, GA) on health, inflammation, and performance. Cattle received either 0 (control) or 10 grams/day Smartamine M, a ruminally protected methionine product. Plasma haptoglobin levels measured on days 0, 14, and 45 were used as a biomarker of inflammation. The Bottom Line: Supplemental methionine supplied by Smartamine M does not improve performance but reduces inflammation and possibly improves immune function in receiving heifers

Zelnate on Arrival Could Decrease the Likelihood of Subsequent Pulls in Suspect Bovine Respiratory Disease Complex Cases

Antimicrobial metaphylaxis is an important tool used for the prevention of Bovine Respiratory Disease Complex; a disease with a large economic impact that typically affects newly-weaned beef calves that are marketed and transported a distance from their origin. There are questions involving the potential benefit of Zelnate, a novel non-antibiotic technology designed to activate an animal’s natural immunity to fight Bovine Respiratory Disease Complex, being used either solely or in combination with metaphylaxis at the time of initial processing of high risk calves. More knowledge is also needed regarding the possible effects of repeated use of Zelnate when subsequent therapy is required in individual Bovine Respiratory Disease Complex cases. The objective of this study was to evaluate the effectiveness of Zelnate when used as part of an antimicrobial metaphylaxis treatment or when used in combination with an antibiotic when a calf is diagnosed with Bovine Respiratory Disease Complex

Horn Fly Control and Growth Implants are Effective Strategies for Heifers Grazing Flint Hills Pasture

Horn flies (Haematobia irritans (L.)) are considered the most important external parasite that negatively affects pasture-based beef systems with losses estimated to exceed $1 billion annually to the U.S. beef industry. Control strategies have relied heavily on insecticide applications to control horn flies and are implemented when the economic threshold of 200 flies/animal have been exceeded. When horn fly populations are maintained below 200 flies/animal by treating them with insecticides then the level of stress annoyance behaviors such as leg stomping, head throwing, and skin twitching decreases while grazing increases. While most stocker operators utilize some type of fly control these are rarely used as a single pharmaceutical technology to aid in performance of the animals. Additional pharmaceutical technologies are utilized in combination of others, with the use of de-wormers and implants showing the largest impact with performance of stockers. The objective of this study was to compare a commercial injectable insecticide, LongRange, to an insecticidal ear tag for horn fly control and determine the impact of weight performance on stockers when fly control technologies were used in combination with implants versus no implants

A simply connected surface of general type with p_g=0 and K^2=2

In this paper we construct a simply connected, minimal, complex surface of general type with p_g=0 and K^2=2 using a rational blow-down surgery and Q-Gorenstein smoothing theory.Comment: 19 pages, 6 figures. To appear in Inventiones Mathematica

Route of Mannheimia haemolytica and Pasteurella multocida Vaccine Administration Does Not Affect Health or Performance of Receiving Heifers

Light weight stocker calves often experience health problems shortly after arrival to feeding facilities. Preventative health programs are routinely administered to calves upon arrival to reduce the incidence of Bovine Respiratory Disease. The major route of vaccine administration in cattle is via injection through either intramuscular or subcutaneous routes. Several products have been introduced that utilize the intranasal route of vaccine administration. There are several reasons why intranasal vaccine administration may be more beneficial: 1) Intranasal vaccine administration alleviates concerns that injections pose for Beef Quality Assurance programs. 2) Intranasal vaccine administration may be less stressful on the animal. 3) Intranasal vaccine administration delivers the vaccine to the site of infection in the case of respiratory pathogens, and may provide a different adaptive immune response to the vaccine. The objective of this study was to determine the effects of route of administration of the Mannheimia haemolytica and Pasteurella multocida fractions of the vaccine regimen on receiving cattle growth performance, health, and mortality

Inhibition of mTOR with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic kidney disease (ADPKD)

Background. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by dysregulated tubular epithelial cell growth, resulting in the formation of multiple renal cysts and progressive renal failure. To date, there is no effective treatment for ADPKD. The mammalian target of rapamycin (mTOR) is an atypical protein kinase and a central controller of cell growth and proliferation. We examined the effect of the mTOR inhibitor sirolimus (rapamycin) on renal functional loss and cyst progression in the Han:SPRD rat model of ADPKD. Methods. Five-week-old male heterozygous cystic (Cy/+) and wild-type normal (+/+) rats were administered sirolimus (2 mg/kg/day) orally through the drinking water for 3 months. The renal function was monitored throughout the treatment phase, and rats were sacrificed thereafter. Kidneys were analysed histomorphometrically, and for the expression and phosphorylation of S6K, a well-characterized target of mTOR in the regulation of cell growth. Results. The steady increase in BUN and creatinine in Cy/+ rats was reduced by 39 and 34%, respectively with sirolimus after 3 months treatment. Kidney weight and 2-kidney/total body weight (2K/TBW) ratios were reduced by 34 and 26% in sirolimus-treated Cy/+ rats. Cyst volume density was also reduced by 18%. Of importance, Cy/+ rats displayed enhanced levels of total and phosphorylated S6K. Sirolimus effectively reduced total and phosphorylated levels of S6K. Conclusion. We conclude that oral sirolimus markedly delays the loss of renal function and retards cyst development in Han:SPRD rats with ADPKD. Our data also suggest that activation of the S6K signalling pathway plays an important role in the pathogenesis of PKD. Sirolimus could be a useful drug to retard progressive renal failure in patients with ADPK

Effects of Limit Feeding Cold Stressed Growing Calves in the Morning Versus the Evening, as well as Bunk Line Sharing on Performance

Objective: To determine the response of cold stressed growing calves to being fed in the evening instead of morning hours, as well as the effect of bunk line sharing. Study Description: Crossbred steers (n = 360) of Texas, Oklahoma, and Idaho origin were blocked by weight into four size groups and randomly assigned to pens, which were randomly allocated to one of five treatments. All steers received a diet formulated to provide 60 Mcal net energy for gain/100 lb of dry matter and were limit fed with a target of 2.0% of their body weight in dry matter intake. Treatments consisted of being fed in the morning (AM), in the evening (PM), fed half of their feed in the morning and half in the evening (50/50), and two treatments that allowed cattle to be fed in the same pen yet were rotated twice daily utilizing a holding pen, allowing for half of the calves to be fed in the morning (Shuttle AM) and half to be fed in the evening (Shuttle PM), doubling the use of the pen and bunk line. The steers were fed for 77 days and individual animal weights were taken on day -1 (allocation), day 0 (initial processing), day 64/65 (blood sampling), and day 77 (final weights). Plasma glucose was obtained individually on day 64 and 65, and pen weights were collected on days 0, 21, 28, 35, 56, 63, 70, and 77. The Bottom Line: When limit feeding cold stressed growing calves, neither shifting from morning feed delivery to evening feed delivery, nor bunk line sharing signifi­cantly improves the efficiency of feed conversion

Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase ρ

Factor-dependent transcription termination mechanisms are poorly understood. We determined a series of cryo–electron microscopy structures portraying the hexameric adenosine triphosphatase (ATPase) ρ on a pathway to terminating NusA/NusG-modified elongation complexes. An open ρ ring contacts NusA, NusG, and multiple regions of RNA polymerase, trapping and locally unwinding proximal upstream DNA. NusA wedges into the ρ ring, initially sequestering RNA. Upon deflection of distal upstream DNA over the RNA polymerase zinc-binding domain, NusA rotates underneath one capping ρ subunit, which subsequently captures RNA. After detachment of NusG and clamp opening, RNA polymerase loses its grip on the RNA:DNA hybrid and is inactivated. Our structural and functional analyses suggest that ρ, and other termination factors across life, may use analogous strategies to allosterically trap transcription complexes in a moribund state