关键词： dryland   India   Prosopis   restoration   woody plant-encroachment  

摘要： Woody plant encroachment is a pervasive global driver impacting grassland structure and functioning, and we know very little about efficacies of management techniques for restoring woody plant-encroached tropical grasslands. In the Banni grasslands of India, which are extensively encroached by an invasive woody legume, Prosopis juliflora, we test the efficacies of two Prosopis management methods-mechanical removal and lopping-to restore native grasslands. Across eight sites in the Banni, using a randomized block design, we monitored herbaceous plant recovery in the two Prosopis management treatments, and an unmanipulated control for 4 years. We also sampled four reference grasslands. We found native herbaceous plant richness and cover to be threefold (mean = 6 species) and sixfold (mean = 18% cover) higher, respectively, in the mechanical-removal treatment compared to the control (mean richness = 2 species, cover = 3%), but found no significant differences between the lopping trsuseatment (mean richness = 5 species, cover = 11%) and the control. While mechanical-removal increased plant diversity, neither management treatment changed the species composition, and both of these treatments were still missing perennial grasses that dominate the reference grasslands. Our data highlight the efficacy of mechanical removal over lopping in restoring native grasslands. However, mechanically removing Prosopis is costly, especially at larger scales. Apart from its detrimental impact on grasslands, Prosopis also has benefits varying with stakeholder groups, and its removal involves complex trade-offs. Until we fully understand the trade-offs involved, it may therefore be better to manage this social-ecological landscape as a mosaic of restored grassland and Prosopis-invaded patches.

关键词： Apparent total tract digestibility   Degradation kinetics   Equine   In-situ   Roughage  

摘要： To evaluate the effect of substituting hay with alternative fibrous feedstuffs, the total collection of faeces was used to measure the apparent total tract digestibility (ATTD). Nutrient disappearance and digestion kinetics were examined with the mobile bag technique (MBT) and marker passage measurements. Four caecally-cannulated horses (body weight (BW) 558 +/- 32 kg) were used in a cross-over design experiment with two periods of 14 days adaptation and four days of faecal collection. Horses were fed three times a day with either a hay-only (HAY) diet or a mixture of hay:supplement (MIX) (15.1 and 8.4:6.7 g dry matter (DM)/kg BW/day, respectively). The hay used in both treatments (HAY and MIX) was mainly of Timothy and first cut. The MIX supplement diet consisted of oat hulls, alfalfa-, sugar beet pulp-(SBP), grass-and soya hull pellets, each given in 0.44 g DM/kg BW/meal. On day 15 in each period, 20 bags of either hay or SBP and 6-12 bags (1x2x12 cm;37 mu m pore size;0.5 g feed) of each feedstuff and ytterbium (Yb, 3 g) were placed in the stomach or caecum, respectively. Bags were harvested from the caecum every hour and faeces were checked for bags every fourth hour, collection time was noted and data from the bags were used to estimate pre-caecal, hindgut and total tract nutrient disappearance. Further, faecal sub samples of 300 g were collected, weighed and stored for Yb analysis and further estimation of feed mean retention time. Rate and extent of feed degradation were estimated from the MBT assuming exponential degradation. The ATTD of DM was similar between the two diets (P > 0.05), but the HAY diet had higher ATTD of crude protein (CP) (P = 0.001), neutral detergent fibre assayed with heat-stable amylase and expressed inclusive of residual ash (aNDF) (P = 0.006), acid detergent fibre (ADF) (P = 0.017), hemicellulose (P = 0.001) and celluloseNDF (P < 0.001). The hindgut mean retention time (MRT) for Yb was longer for the MIX than the HAY diet (P < 0.001).

关键词： Language   Functional laterality   Brain neoplasms   Cerebellum   Magnetic resonance imaging  

摘要： Objectives Crossed cerebro-cerebellar BOLD activations have recently come to light as additional diagnostic features for patients with brain tumors. The covert verb generation (VG) task is a widely used language paradigm to determine these language-related crossed activations. Here we demonstrate these crossed activations in two additional language paradigms, the semantic and phonological association tasks. We propose the merit of these tasks to language lateralization determination in the clinic as they are easy to monitor and suitable for patients with aphasia. Methods Patients with brain tumors localized at different cortical sites (n = 71) performed three language paradigms, namely the VG task as well as the semantic (SA) and phonological (PA) association tasks with button-press responses. Respective language activations in disparate cortical regions and the cerebellum were assigned laterality. Agreements in laterality between the two new tasks and the verb generation task were tested using Cohen's kappa. Results Both tasks significantly agreed in cortical and cerebellar lateralization with the verb generation task in patients. Additionally, a McNemar test confirmed the presence of crossed activations in the cortex and the cerebellum in the entire subject population. Conclusion We demonstrated that the semantic and phonological association tasks resulted in crossed cerebro-cerebellar language lateralization activations as those observed due to the covert verb generation task. This may suggest the possibility of these tasks being used conjointly with the traditional verb generation task, especially for subjects that may be unable to perform the latter.

关键词： alternative splicing   carcinogenesis   chemotherapy   cholangiocarcinoma   hepatocellular carcinoma   metastasis   multidrug resistance  

摘要： Simple Summary Among the top ten deadly solid tumors are the two most frequent liver cancers, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma, whose development and malignancy are favored by multifactorial conditions, which include aberrant maturation of pre-mRNA due to abnormalities in either the machinery involved in the splicing, i.e., the spliceosome and associated factors, or the nucleotide sequences of essential sites for the exon recognition process. As a consequence of cancer-associated aberrant splicing in hepatocytes- and cholangiocytes-derived cancer cells, abnormal proteins are synthesized. They contribute to the dysregulated proliferation and eventually transformation of these cells to phenotypes with enhanced invasiveness, migration, and multidrug resistance, which contributes to the poor prognosis that characterizes these liver cancers. The two most frequent primary cancers affecting the liver, whose incidence is growing worldwide, are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), which are among the five most lethal solid tumors with meager 5-year survival rates. The common difficulty in most cases to reach an early diagnosis, the aggressive invasiveness of both tumors, and the lack of favorable response to pharmacotherapy, either classical chemotherapy or modern targeted therapy, account for the poor outcome of these patients. Alternative splicing (AS) during pre-mRNA maturation results in changes that might affect proteins involved in different aspects of cancer biology, such as cell cycle dysregulation, cytoskeleton disorganization, migration, and adhesion, which favors carcinogenesis, tumor promotion, and progression, allowing cancer cells to escape from pharmacological treatments. Reasons accounting for cancer-associated aberrant splicing include mutations that create or disrupt splicing sites or splicing enhancers or silencers, abnormal expression of splicing factors, and impaired signaling pathways af

关键词： multisystem inflammatory syndrome in children (MIS-C)   COVID-19   pediatrics   diagnosis   management   New York  

摘要： On March 20, 2021, the Columbia University Department of Anesthesiology hosted the Papper virtual event dedicated to an academic discussion of various aspects of coronavirus disease-2019. Dr. Eva Cheung, a pediatric intensivist and pediatric cardiologist, spoke about the clinical challenges associated with tackling multisystem inflammatory syndrome in children, a novel clinical entity in pediatric patients related to coronavirus disease-2019, and the experience with confronting multisystem inflammatory syndrome in children in New York.

关键词： Genomics   RNA   RNA metabolism   Life Sciences   general   Biochemistry   Protein Structure   Membrane Biology   Biological Microscopy  

摘要： Analogous to alternative splicing, alternative polyadenylation (APA) has long been thought to occur independently at proximal and distal polyA sites. Using fractionation-seq, we unexpectedly identified several hundred APA genes in human cells whose distal polyA isoforms are retained in chromatin/nuclear matrix and whose proximal polyA isoforms are released into the cytoplasm. Global metabolic PAS-seq and Nanopore long-read RNA-sequencing provide further evidence that the strong distal polyA sites are processed first and the resulting transcripts are subsequently anchored in chromatin/nuclear matrix to serve as precursors for further processing at proximal polyA sites. Inserting an autocleavable ribozyme between the proximal and distal polyA sites, coupled with a Cleave-seq approach that we describe here, confirms that the distal polyA isoform is indeed the precursor to the proximal polyA isoform. Therefore, unlike alternative splicing, APA sites are recognized independently, and in many cases, in a sequential manner. This provides a versatile strategy to regulate gene expression in mammalian cells. New data reveal a sequential mode of alternative polyadenylation. Distal polyA sites are processed first and the resultant transcripts are retained in the nuclear-chromatin matrix for subsequent cleavage and polyadenylation at proximal polyA sites.

关键词： mitochondrial potassium channels   cytoprotection   mitochondria   potassium channel openers  

摘要： Mitochondrial potassium channels control potassium influx into the mitochondrial matrix and thus regulate mitochondrial membrane potential, volume, respiration, and synthesis of reactive oxygen species (ROS). It has been found that pharmacological activation of mitochondrial potassium channels during ischemia/reperfusion (I/R) injury activates cytoprotective mechanisms resulting in increased cell survival. In cancer cells, the inhibition of these channels leads to increased cell death. Therefore, mitochondrial potassium channels are intriguing targets for the development of new pharmacological strategies. In most cases, however, the substances that modulate the mitochondrial potassium channels have a few alternative targets in the cell. This may result in unexpected or unwanted effects induced by these compounds. In our review, we briefly present the various classes of mitochondrial potassium (mitoK) channels and describe the chemical compounds that modulate their activity. We also describe examples of the multidirectional activity of the activators and inhibitors of mitochondrial potassium channels.

关键词： APEX   Calf weight gain algorithm   Multiple-paddock rotation grazing   Continuous grazing   Economic income   Stocking density  

摘要： CONTEXT: Simulation tools are increasingly used to inform grazing management decisions by assessing livestock performance, as well as environmental and economic impacts. Ability to represent the grazing of multiple pastures (i.e., paddocks) that differ in soil, hydrology, vegetation, and management is critical for reliable grazing management decision support. OBJECTIVE: The main objectives of this study were to: 1) modify APEX (Agricultural Policy/Environmental eXtender) for sub-daily grazing, cow-calf weight gain, and supplemental hay, and 2) evaluate the APEX modifications in terms of simulating biomass, calf weight gain, economic impacts of alternative cow-calf grazing management strategies. METHODS: APEX was modified to enhance its ability to simulate alternative grazing management strategies by including sub-daily grazing among multiple paddocks, supplemental hay estimation, and optional simulation of cow-calf weight gain based either on energy or total digestible nutrients (TDN). Simulation results were evaluated against a 5-year experimental data set from Central Texas comparing multi-paddock rotational grazing and conventional continuous grazing. RESULTS AND CONCLUSION: The modified APEX model adequately simulated the responses of vegetation biomass (coefficient of determination, R-2 = 0.60-0.70), hay consumption (R-2 = 0.94-0.95), calf weaning weight (R-2 = 0.52-0.65), costs (R-2 = 0.98), and profits (R-2 = 0.89) to the two grazing treatments across years. Simulations with the energy-based weight gain algorithm showed more pronounced effects on above-ground biomass, whereas the TDN-based algorithm had a more pronounced weight gain response to forage intake and hay quality. No significant differences (p > 0.05) in biomass and calf weaning weight were observed between treatments across the years for measured data and for energy-based APEX simulation;however, the TDN-based algorithm simulated lower calf weaning weight in multi-paddock rotational grazing than i

关键词： AP50   CH50   alternative pathway activity   reference interval   total hemolytical complement activity  

关键词： clinical trial simulation   Crohn's disease   pharmacometrics   population pharmacokinetics-pharmacodynamics   ustekinumab  

摘要： Aims: In the UNITI endoscopy sub-study, only 17.4% of patients with Crohn's disease (CD) on ustekinumab achieved endoscopic response and 10.9% of patients achieved endoscopic remission at week (w)44. We aimed to evaluate the impact of alternative ustekinumab dosage regimens on endoscopic outcomes based on population pharmacokinetic-pharmacodynamic (popPK-PD) modelling and simulation analysis. Methods: Real-world data were obtained from 83 patients with moderate-to-severe CD (95% biological-refractory) enrolled in a prospective cohort study receiving intravenous ustekinumab (similar to 6 mg/kg) followed by every eight-week (q8w) subcutaneous maintenance therapy (90 mg). Three sequential models were developed: a two-compartment popPK model linking ustekinumab dose to ustekinumab exposure, an indirect response popPK-PD model describing the effect of ustekinumab exposure on fecal calprotectin (fCal), and a logistic regression outcome model linking fCal to endoscopic outcomes. Results: Ustekinumab clearance increased with decreasing serum albumin and increasing bodyweight. fCal decreased with increasing ustekinumab exposure. The probability of endoscopic response at w24 increased from 10.0% to 17.9% with fCal at w8 decreasing from 1800 mu g/g to 694 mu g/g (EC50). The probability of endoscopic remission at w24 increased from 2.1% to 10.0% with fCal at w8 decreasing from 1800 mu g/g to 214 mu g/g (EC50). Simulation-based comparison of q8w and q4w maintenance dosing regimens predicted 16.7% and 22.2% endoscopic response rates, respectively. Endoscopic remission rates were estimated to be 4.2% on q8w dosing and 6.7% on q4w dosing. Conclusions: The developed models can guide clinical trial design and support model-informed dose optimization (stratified or individualized dosing) to improve endoscopic outcomes.