Alternative Splicing and Polyadenylation Contribute to the Generation of hERG1 C-terminal Isoforms

The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel. Several hERG1 isoforms with different N- and C-terminal ends have been identified. The hERG1a, hERG1b, and hERG1-3.1 isoforms contain the full-length C terminus, whereas the hERG1USOisoforms, hERG1aUSO and hERG1bUSO, lack most of the C-terminal domain and contain a unique C-terminal end. The mechanisms underlying the generation of hERG1USOisoforms are not understood. We show that hERG1 isoforms with different C-terminal ends are generated by alternative splicing and polyadenylation of hERG1 pre-mRNA. We identified an intrinsically weak, noncanonical poly(A) signal, AGUAAA, within intron 9 of hERG1 that modulates the expression of hERG1a and hERG1aUSO. Replacing AGUAAA with the strong, canonical poly(A) signal AAUAAA resulted in the predominant production of hERG1aUSO and a marked decrease in hERG1 current. In contrast, eliminating the intron 9 poly(A) signal or increasing the strength of 5′ splice site led to the predominant production of hERG1a and a significant increase in hERG1 current. We found significant variation in the relative abundance of hERG1 C-terminal isoforms in different human tissues. Taken together, these findings suggest that post-transcriptional regulation of hERG1 pre-mRNA may represent a novel mechanism to modulate the expression and function of hERG1 channels

X-ray observations of the galaxy cluster PKS 0745-191: To the virial radius, and beyond

We measure X-ray emission from the outskirts of the cluster of galaxies PKS 0745-191 with Suzaku, determining radial profiles of density, temperature, entropy, gas fraction, and mass. These measurements extend beyond the virial radius for the first time, providing new information about cluster assembly and the diffuse intracluster medium out to ~1.5 r_200, (r_200 ~ 1.7 Mpc ~ 15'). The temperature is found to decrease by roughly 70 per cent from 0.3-1 r_200. We also see a flattening of the entropy profile near the virial radius and consider the implications this has for the assumption of hydrostatic equilibrium when deriving mass estimates. We place these observations in the context of simulations and analytical models to develop a better understanding of non-gravitational physics in the outskirts of the cluster.Comment: 10 pages, 11 figures, accepted to MNRAS; expanded discussion of analysis and uncertainties, results qualitatively unchange

Off-Stream Water, Shade and Nutritional Supplementation to Modify Animal Behavior

Another way to manage pasture water for positive water quality is to modify animal behavior. Find out about providing off-stream water, shade, and nutritional supplementation.https://lib.dr.iastate.edu/extension_ag_pubs/1224/thumbnail.jp

Anterior cruciate ligament reconstruction with bone-patellar tendon-bone autograft versus allograft in young patients

Objectives: Traditionally, bone-patella tendon-bone (BTB) autograft has been the gold standard graft choice for younger, athletic patients requiring ACL reconstruction. However, donor site morbidity, post-operative patella fracture, and increased operative time have led many surgeons to choose BTB allograft for their reconstructions. Opponents of allografts feel that slower healing time, higher rate of graft failure, and potential for disease transmission makes them undesirable graft choices in athletic patients. The purpose of this study is to evaluate the clinical outcomes, both subjective and objective, of young patients that who have undergone either BTB autograft or allograft reconstructions with a minimum of 2-year follow-up. Methods: One hundred and twenty patients (60 autograft, 60 allograft), age 25 and below at time of surgery, were contacted after being retrospectively identified as patients having an ACL reconstruction with either a BTB allograft or autograft by one senior surgeon. Patients were administered the Lysholm Knee Scoring Scale and IKDC Subjective Knee Evaluation questionnaires. Fifty (25 BTB autograft and 25 BTB allograft) of the 120 returned for physical examination as well as completion of a single leg hop test and laxity evaluation using a KT-1000 arthrometer evaluation. Of the 120 patients contacted, there were a total of 7 failures (5.8%) requiring revision, 6 in the allograft group (86%) and 1 in the autograft group (14%). Results: The average Lysholm scores were 89.0 and 89.56 and the average IKDC scores were 90.8 and 92.1 in the autograft and allograft groups respectively. The differences in the Lysholm scores and the IKDC scores were not significant. The single leg hop and KT-1000 scores were also not significantly different. One autograft patient had a minor motion deficit. Three allograft patients had a grade 1 Lachman and pivot glide. One autograft patient and two allograft patients had mild patellafemoral crepitus. There was no significant difference in anterior knee pain between the two groups Conclusion: There is no significant difference in patient-rated outcome between ACL reconstructions using BTB autografts versus allografts. However, the overall study group did reveal an increased failure rate requiring revision in the allograft group. © The Author(s) 2015

Evaluation of Stockpiled Berseem Clover and Brown Midrib Sorghum x Sudangrass as Supplements for Grazed Cornstalks in Beef Cow Wintering Systems

Berseem clover and oats were incorporated into a corn-oat/berseem clover rotation in 1994-1996. Two cuttings of oat-berseem clover hay were harvested during the summer before forage was stockpiled for winter grazing. In 1995, brown midrib sorghum x sudangrass hybrid was seeded into a field adjacent to a corn field. This was repeated in 1996 with a standard sorghum x sudangrass hybrid. After corn harvest in 1994–1996, Charolais x Angus x Simmental cows and heifers in midgestation were allotted to corn crop residue, corn crop residue-berseem clover, and corn crop residue-sorghum x sudangrass fields at 2.5 acres/cow, or to a drylot. Berseem clover had greater concentration of digestible organic matter and crude protein than corn crop residues. Corn crop residue digestible organic matter concentration was lower than berseem clover and the brown midrib sorghum x sudangrass, but was higher than that of the standard sorghum x sudangrass hybrid in 1996. Cows grazing corn crop residues without complementary forages required an average of 2,374 less lb. hay per cow than cows maintained in a drylot in 1994-1996. In 1994 and 1996, simultaneous grazing of berseem clover with corn crop residues did not reduce hay feeding more than feeding corn crop residues alone, yet did significantly reduce the amount of hay needed in 1995 to maintain cows by 358 and 376 lb. hay per cow compared with grazing corn crop residues without complementary forage

MDACE: MIMIC Documents Annotated with Code Evidence

We introduce a dataset for evidence/rationale extraction on an extreme multi-label classification task over long medical documents. One such task is Computer-Assisted Coding (CAC) which has improved significantly in recent years, thanks to advances in machine learning technologies. Yet simply predicting a set of final codes for a patient encounter is insufficient as CAC systems are required to provide supporting textual evidence to justify the billing codes. A model able to produce accurate and reliable supporting evidence for each code would be a tremendous benefit. However, a human annotated code evidence corpus is extremely difficult to create because it requires specialized knowledge. In this paper, we introduce MDACE, the first publicly available code evidence dataset, which is built on a subset of the MIMIC-III clinical records. The dataset -- annotated by professional medical coders -- consists of 302 Inpatient charts with 3,934 evidence spans and 52 Profee charts with 5,563 evidence spans. We implemented several evidence extraction methods based on the EffectiveCAN model (Liu et al., 2021) to establish baseline performance on this dataset. MDACE can be used to evaluate code evidence extraction methods for CAC systems, as well as the accuracy and interpretability of deep learning models for multi-label classification. We believe that the release of MDACE will greatly improve the understanding and application of deep learning technologies for medical coding and document classification

Evaluation of a Year-Round Grazing System: Winter Progress Report

The winter component of a year-round grazing system involving grazing of corn crop residues followed by grazing stockpiled grass legume forages was compared at the McNay Research Farm with that of the winter component of a minimal land system that maintained cows in drylot,. In the summer of 1995, two cuttings of hay were harvested from two 15-acre fields containing “Johnston” endophyte-free tall fescue and red clover, and two cuttings of hay were taken from two 15-acre fields of smooth bromegrass and red clover. Hay yields were 4,236 and 4,600 pounds of dry matter per acre for the tall fescue--red clover and smooth bromegrass--red clover. Following grain harvest four 7.5-acre fields containing corn crop residue were stocked with cows at midgestation at an allowance of 1.5 acres per cow. Forage yields at the initiation of corn crop grazing were 3,766pounds of dry matter per acre for corn crop residue, 1,748 pounds for tall fescue--red clover, and 1,.880 pounds for smooth bromegrass--red clover. Corn crop residues and stockpiled forages were grazed in a strip stocking system. For comparison, 20 cows were placed in two drylots simultaneously to the initiation of corn crop grazing where they remained throughout the winter and spring grazing seasons. Cows maintained in drylot or grazing corn crop residue and stockpiled forages were supplemented with hay as large round bales to maintain a body condition score of five. No seasonal differences in body weight and body condition were observed between grazing cows or cows maintained in drylot, but grazing cows required 87% and 84% less harvested hay than cows in drylot during the winter and spring respectively. Because less hay was needed to maintain grazing cows, an excess of 11,905 and 12,803 pounds of hay dry matter per cow remained in the year-round grazing system. During corn crop grazing, organic matter yield decreased at 27.3 pounds of organic matter per day from grazed areas of corn crop residue. Organic matter losses due to weathering were 9.4, 12.9, and 15.8 pounds per day in corn crop residue, tall fescue-red clover and smooth bromegrass-red clover. Organic matter losses from grazed and ungrazed areas during stockpiled grazing were 7.3 and 6.9 for tall fescue--red clover and 2.1, 2.9 for smooth bromegrass--red clover

Effects of Grazing Management on Forage Sward Height, Mass, and Nutrient Concentrations and the Proportions of Fecal Cover and Bare Soil in Pastures

Grazing management can alter the characteristics of the pasture sward. Changes in pasture forage characteristics can affect both the nutritional value of the forage and the environmental impacts of the grazing system. Six 30-acre cool-season grass pastures, containing predominantly smooth bromegrass and bisected by a 642-foot stream segment were grouped into two blocks and assigned one of three treatments: continuous stocking - unrestricted stream access (CSU), continuous stocking - restricted stream access (CSR), and rotational stocking (RS). Forage sward height and mass along with the proportion of bare ground and fecal cover were determined monthly from open and congregation areas within four zones in the pasture. Zones were defined as on the stream bank (bank), from the stream bank to 110 feet from the stream bank (110), 110 feet to 220 feet from the stream bank (220), and greater than 220 feet from the stream bank (upland). Forage samples were analyzed for in vitro dry matter digestibility (IVDMD), crude protein (CP), and phosphorus (P). The occurrence of bare ground and fecal cover was greater in congregation areas than open areas across all pastures. Bare ground was greater along the banks in all grazing management practices but was not different between pastures in the 110, 220, or upland zones. Mean forage CP concentrations were greater and P concentrations tended to be greater in the RS pastures than in CSU or CSR pastures

Evaluation of a Year-Round Grazing System: Summer Cow-Calf Progress Report

A comparison was made between two different summer grazing systems. One system was the summer component of a year-round grazing system, involving the rotational stocking of smooth bromegrass--orchardgrass--birdsfoot trefoil pastures and winter stockpiles pastures with cowcalf pairs co-grazing with stocker yearlings at .75 animal units per acre. That system was compared with a minimal land system involving the rotational stocking of smooth bromegrass--orchardgrass-- birdsfoot trefoil summer pastures with cow-calf pairs grazing at .64 animal units per acre and hay removal from 25% of the pasture. Stocker yearlings or hay removal were used as management tools to remove excess forage and optimize forage quality. Hay was removed once from three fourths of the winter stockpiled pastures and one fourth of the allocated summer pastures. Cow-calf pairs grazing in the year-round system utilized on fourth of the winter stockpile pastures due to lack of forage, whereas cow-calf pairs grazing with hay removal were supplemented with harvested hay for two weeks during the summer. Grazing system did not affect cow body weight, condition score, or daily calf weight gain. Growing animal production per acre was affected by grazing system, with the minimal land system having a higher production level