Understanding metabolism in the pathogen Candida glabrata is key to identifying new targets for antifungals. The thiamine biosynthetic (THI) pathway is partially defective in C. glabrata, but the ...transcription factor CgPdc2 upregulates some thiamine biosynthetic and transport genes. One of these genes encodes a recently evolved thiamine pyrophosphatase (CgPMU3) that is critical for accessing external thiamine. Here, we demonstrate that CgPdc2 primarily regulates THI genes. In Saccharomyces cerevisiae, Pdc2 regulates both THI and pyruvate decarboxylase (PDC) genes, with PDC proteins being a major thiamine sink. Deletion of PDC2 is lethal in S. cerevisiae in standard growth conditions, but not in C. glabrata. We uncover cryptic cis elements in C. glabrata PDC promoters that still allow for regulation by ScPdc2, even when that regulation is not apparent in C. glabrata. C. glabrata lacks Thi2, and it is likely that inclusion of Thi2 into transcriptional regulation in S. cerevisiae allows for a more complex regulation pattern and regulation of THI and PDC genes. We present evidence that Pdc2 functions independent of Thi2 and Thi3 in both species. The C-terminal activation domain of Pdc2 is intrinsically disordered and critical for species differences. Truncation of the disordered domains leads to a gradual loss of activity. Through a series of cross species complementation assays of transcription, we suggest that there are multiple Pdc2-containing complexes, and C. glabrata appears to have the simplest requirement set for THI genes, except for CgPMU3. CgPMU3 has different cis requirements, but still requires Pdc2 and Thi3 to be upregulated by thiamine starvation. We identify the minimal region sufficient for thiamine regulation in CgTHI20, CgPMU3, and ScPDC5 promoters. Defining the cis and trans requirements for THI promoters should lead to an understanding of how to interrupt their upregulation and provide targets in metabolism for antifungals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiopulmonary exercise testing (CPET) is an established method for evaluating dyspnea and ventilatory abnormalities. Ventilatory reserve is typically assessed as the ratio of peak exercise ...ventilation to maximal voluntary ventilation. Unfortunately, this crude assessment provides limited data on the factors that limit the normal ventilatory response to exercise. Additional measurements can provide a more comprehensive evaluation of respiratory mechanical constraints during CPET (e.g., expiratory flow limitation and operating lung volumes). These measurements are directly dependent on an accurate assessment of inspiratory capacity (IC) throughout rest and exercise. Despite the valuable insight that the IC provides, there are no established recommendations on how to perform the maneuver during exercise and how to analyze and interpret the data. Accordingly, the purpose of this manuscript is to comprehensively examine a number of methodological issues related to the measurement, analysis, and interpretation of the IC. We will also briefly discuss IC responses to exercise in health and disease and will consider how various therapeutic interventions influence the IC, particularly in patients with chronic obstructive pulmonary disease. Our main conclusion is that IC measurements are both reproducible and responsive to therapy and provide important information on the mechanisms of dyspnea and exercise limitation during CPET.
The objectives of this study were to evaluate the influence of RFI and cow age on the supplement intake and grazing behavior of beef cattle. Average daily supplement intake (kg/cow/d) displayed an ...RFI × cow age interaction (
< 0.01), with a linear increase in average daily supplement intake with increasing RFI of 3-year-old cows (
< 0.01). Average daily supplement intake (g ∙ kg BW
∙ d
) displayed an RFI × cow age interaction (
< 0.01), with a quadratic effect on supplement intake of 3-year-old cows (
= 0.01). Cow age displayed a quadratic effect on variation of supplement intake (
< 0.01), where 1-year-old cows had a greater CV of supplement intake than all other cow ages (
< 0.01). Distance traveled displayed a cow age × RFI interaction (
= 0.02), where high-RFI 5-year-old cows traveled further per day than low 5-year-old RFI cows. The probability of grazing site selection was influenced by cow age (
≤ 0.03). In summary, heifer post-weaning RFI had minimal effects on beef cattle performance, grazing behavior, or resource utilization; however, cow age impacted both grazing behavior and resource use.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
This study evaluated the influence of cow age and temperature adjusted for wind chill (Twindchill) on supplement intake behavior of beef cattle winter grazing northern mixed grass prairie ...rangelands. A commercial herd of 272 (year 1) and 302 (year 2) bred cows (Angus, Simmental × Angus) ranging in age from 1- to 12-yr-old grazed a 329-ha rangeland pasture (~1.5 ha animal unit monthˉ 1) from November to January. Cows were grouped into seven age classes (1 yr old, 2 yr old, 3 yr old, 4 yr old, 5 yr old, 6 yr old, and ≥ 7 yr old) and were provided free-choice access to a 30% CP self-fed canola meal-based pelleted supplement with 25% salt to limit intake. The target daily intake was 0.91 kg cowˉ 1 dˉ 1. Supplement was provided in a SmartFeed Pro self-feeder system to measure individual animal supplement intake and behavior. An Onset HOBO U30-NRC Weather Station was placed near the supplement feeders to collect weather data for the entirety of the grazing period. Average daily supplement intake and the coefficient variation in supplement intake displayed a Twindchill × cow age × year interaction (P ≤ 0.02). There was a negative linear effect of age on supplement intake (kg cowˉ 1 dˉ 1) for days with below average Twindchill conditions in both years (P < 0.01). There was also negative linear effect of age on supplement intake (g kg of BWˉ 1 dˉ 1) at average Twindchill in year 1 and below average Twindchill in year 2 (P < 0.01). Cow age had a quadratic effect on supplement intake for days with below average Twindchill in year 1 (P = 0.02); however, this was a curvilinear response where yearlings and 2-yr-olds consumed more supplement per kilogram of BW than other age cattle (P < 0.01). Cow age had positive linear effects on variation in supplement intake at below average Twindchill conditions in both years (P < 0.01). Daily visits to the supplement feeders displayed a Twindchill × cow age interaction (P < 0.01), where there was a linear decrease in visits with increasing age at below average Twindchill conditions (P < 0.01). In summary, both cow age and the winter environmental conditions interacted to influence animal supplement intake behavior and, as a result, nutrient delivery efficacy in winter grazing beef cattle.
Purpose
Clinical equipoise exists with the use of novel reperfusion therapies such as catheter-directed thrombolysis in the management of patients presenting to hospital with high risk pulmonary ...embolism (PE). Therapeutic options rely on clinical presentation, patient factors, physician preference, and institutional availability. We established a Pulmonary Embolism Response Team (PERT) to provide urgent assessment and multidisciplinary care for patients presenting to our institution with high-risk PE.
Methods
Data were retrospectively collected from PERT activations between January 2016 and December 2018. Chi square tests were used to determine differences in mortality across the three years of study. Logistic regression was used to evaluate 30- and 90-day mortality and occurrence of major bleeds between those receiving anticoagulation alone (AC) and those receiving advanced reperfusion therapy (ART).
Results
There were 128 PERT activations over three years, the majority originating from the emergency department. Eighty-five percent of activations were for submassive PE, with 56% of all activations assessed as submassive-high risk. Fifteen patients (12%) presented with massive PE. Advanced reperfusion therapy was used in 29 (23%) patients, of whom 25 (20%) received catheter-directed thrombolysis. There was an increased risk of major bleeding in the ART group compared with in the AC group (odds ratio
OR, 17.9; 95% confidence interval CI, 4.1 to 125.0;
P
< 0.001), but no increased risk of mortality at 30 days (OR, 2.1; 95% CI, 0.4 to 9.1;
P
= 0.3). The 30-day mortality rate was 7.8%.
Conclusion
We describe the first Canadian PERT, a multidisciplinary team aimed at providing urgent individualized care for patients with high-risk PE. Further research is necessary to determine whether a PERT improves clinical outcomes.
Comprehensive cow-calf production data was utilized to evaluate the impact of dam age on lifetime productivity of Angus replacement beef females. Cows used in this study were commercial Angus ...replacement females born between 2006 and 2020, ranging in age from 1 to 14-yr of age (n = 3568). To determine the impact of dam age on lifetime productivity, cows were classified by age groups, specifically 2-, 3-, 4-, 5-, 6/7-, and 8-yrs old and older. The 8-yr and older group consisted of females that were up to 14-yr of age. Cow BW at breeding exhibited a cow age × dam age interaction (p < 0.01). Cows at 5-yrs of age from 2-yr old dams weighed less at breeding than cows at 5-yrs of age from 3-, 4-, 5- and 8-years and older dams, with cows at 5-yr of age from 6/7-yr old dams being intermediate. The probability of remaining in the herd at the age of 5 was significant for dam age (p = 0.05) averaging 69.41%, but after further delineation, no significant impacts of dam age were observed. Productivity as a measure of total pounds of calf weaned through 5-yrs displayed a dam age effect (p = 0.01) with cows from 8-yrs or older dams weaning more total pounds of calf, than cows from 3-yr-old dams. In summary, the impact of dam age on lifetime productivity indicates that dam age can impact future productivity of their offspring.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We evaluated heifer post-weaning residual feed intake (RFI) classification and cow age on dry matter intake (DMI) at two stages of production. Fifty-nine non-lactating, pregnant, (Study 1) and ...fifty-four lactating, non-pregnant (Study 2) commercial black Angus beef cows were grouped by age and RFI. Free-choice, hay pellets were fed in a GrowSafe feeding system. In Study 1, cow DMI (kg/d) and intake rate (g/min) displayed a cow age effect (p < 0.01) with an increase in DMI and intake rate with increasing cow age. In Study 2, cow DMI (kg/d) and intake rate (g/min) displayed a cow age effect (p < 0.02) with an increase in DMI and intake rate with increasing cow age. Milk production displayed a cow age × RFI interaction (p < 0.01) where both 5–6-year-old and 8–9-year-old low RFI cows produced more milk than high RFI cows. For both studies, intake and intake behavior were not influenced by RFI (p ≥ 0.16) or cow age × RFI interaction (p ≥ 0.21). In summary, heifer’s post-weaning RFI had minimal effects on beef cattle DMI or intake behavior, however, some differences were observed in milk production.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A significant welfare concern for those within the horse industry is that of the overpopulation in free-roaming horses in the western US. The goal of the present study was to identify a humane and ...inexpensive means of providing contraception and reducing pregnancy rates in a way that could be applied to free-roaming horses on the western U.S. open range lands. A series of studies was conducted utilizing the previously-described silastic O-ring intrauterine devices (IUDs). Throughout these studies pregnancy was successfully prevented in mares with an O-ring IUD, but collective retention rates failed to exceed 50% regardless of size or durometer (material hardness/malleability). When the O-ring IUDs were compared to the recently-described Y-design IUDs (Holyoak et al., 2021) the Y-design IUDs had a markedly greater rate of retention; therefore, the Y-design IUDs would be most appropriate for potential use in free-roaming horses. Assessment of mare records revealed that the vast majority of mares continued to have ovulations and mating continued to occur while the IUDs were in place. A few mares had multiple small ovarian follicles when the IUD was in utero. Findings indicate that utilizing an IUD with the expectation of estrus suppression in mares would fail to be fruitful.
•IUDs did not provide estrus suppression in mares.•O-ring IUDs were unable to obtain greater than 50% retention in utero.•Y-design IUDs are a feasible method of providing contraception to free-roaming horses in efforts to improve animal welfare.•Objective data related to IUDs and improvement in mare performance is currently lacking.
Understanding sex differences in the qualitative dimensions of exertional dyspnea may provide insight into why women are more affected by this symptom than men. This study explored the evolution of ...the qualitative dimensions of dyspnea in 70 healthy, young, physically active adults (35 M and 35 F). Participants rated the intensity of their breathing discomfort (Borg 0-10 scale) and selected phrases that best described their breathing from a standardized list (work/effort, unsatisfied inspiration, and unsatisfied expiration) throughout each stage of a symptom-limited incremental-cycle exercise test. Following exercise, participants selected phrases that described their breathing at maximal exercise from a list of 15 standardized phrases. Intensity of breathing discomfort was significantly higher in women for a given ventilation, but differences disappeared when ventilation was expressed as a percentage of maximum voluntary ventilation. The dominant qualitative descriptor in both sexes throughout exercise was increased work/effort of breathing. At peak exercise, women were significantly more likely to select the following phrases: "my breathing feels shallow," "I cannot get enough air in," "I cannot take a deep breath in," and "my breath does not go in all the way." Women adopted a more rapid and shallow breathing pattern and had significantly higher end-inspiratory lung volumes relative to total lung capacity throughout exercise relative to men. These findings suggest that men and women do not differ in their perceived quality of dyspnea during submaximal exercise, but subjective differences appear at maximal exercise and may be related, at least in part, to underlying sex differences in breathing patterns and operating lung volumes during exercise.
PDF
