scholarly journals Mining divergent and conserved signals in 5′ splicing site sequences

2021 ◽  
Author(s):  
Maximiliano Beckel ◽  
Bruno Kaufman ◽  
Marcelo Yanovsky ◽  
Ariel Chernomoretz
Keyword(s):  
Splicing Factors ◽  
Splicing Regulation ◽  
Frequency Of Occurrence ◽  
Unified Framework ◽  
Modeling Framework ◽  
Sequence Composition ◽  
Maximum Entropy Modeling ◽  
Gene Architecture ◽  
The Relationship ◽  
Splicing Site

Despite the fact that the main steps of the splicing process are similar across eukaryotes, differences in splicing factors, gene architecture and sequence divergences in splicing signals suggest clade-specific features of splicing and its regulation. In this work we study conserved and divergent signatures embedded in the sequence composition of eukaryotic 5′ splicing sites. We considered a regularized maximum entropy modeling framework to mine for non-trivial two-site correlations in donor sequences of 14 different eukaryote organisms. Our approach allowed us to accommodate and extend, within a unified framework, many of the regularities observed in previous works like the relationship between the frequency of occurrence of natural sequences and the corresponding site's strength, or the negative epistatic effects between exonic and intronic consensus sites. In addition, performing a systematic and comparative analysis of 5′ss we showed that lineage information could be traced not only from single-site frequencies but also from joint di-nucleotide probabilities of donor sequences. Noticeably, we could also identify specific two-site coupling patterns for plants and for animals and argue that these differences, in association with taxon-specific features involving U6 snRNP, could be the basis for differences in splicing regulation previously reported between these groups.

scholarly journals High coverage COVID-19 mRNA vaccination rapidly controls SARS-CoV-2 transmission in long-term care facilities

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Pablo M. De Salazar ◽  
Nicholas B. Link ◽  
Karuna Lamarca ◽  
Mauricio Santillana
Keyword(s):  
Long Term Care ◽  
Mitigation Strategies ◽  
Key Factors ◽  
Modeling Framework ◽  
High Coverage ◽  
Term Care ◽  
Early Effect ◽  
Care Facilities ◽  
The Relationship

Abstract Background Residents of Long-Term Care Facilities (LTCFs) represent a major share of COVID-19 deaths worldwide. Measuring the vaccine effectiveness among the most vulnerable in these settings is essential to monitor and improve mitigation strategies. Methods We evaluate the early effect of the administration of BNT162b2-mRNA vaccine to individuals older than 64 years residing in LTCFs in Catalonia, Spain. We monitor all the SARS-CoV-2 documented infections and deaths among LTCFs residents once more than 70% of them were fully vaccinated (February–March 2021). We develop a modeling framework based on the relationship between community and LTCFs transmission during the pre-vaccination period (July–December 2020). We compute the total reduction in SARS-CoV-2 documented infections and deaths among residents of LTCFs over time, as well as the reduction in the detected transmission for all the LTCFs. We compare the true observations with the counterfactual predictions. Results We estimate that once more than 70% of the LTCFs population are fully vaccinated, 74% (58–81%, 90% CI) of COVID-19 deaths and 75% (36–86%, 90% CI) of all expected documented infections among LTCFs residents are prevented. Further, detectable transmission among LTCFs residents is reduced up to 90% (76–93%, 90% CI) relative to that expected given transmission in the community. Conclusions Our findings provide evidence that high-coverage vaccination is the most effective intervention to prevent SARS-CoV-2 transmission and death among LTCFs residents. Widespread vaccination could be a feasible avenue to control the COVID-19 pandemic conditional on key factors such as vaccine escape, roll out and coverage.

scholarly journals Regulation of RNA Splicing: Aberrant Splicing Regulation and Therapeutic Targets in Cancer

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 923
Author(s):  
Koji Kitamura ◽  
Keisuke Nimura
Keyword(s):  
Dna Sequences ◽  
Rna Splicing ◽  
Splicing Factors ◽  
Splicing Regulation ◽  
Aberrant Splicing ◽  
Aberrant Expression ◽  
Non Coding Rnas ◽  
Precursor Mrna ◽  
Splicing Enhancer ◽  
Small Nuclear Ribonucleoproteins

RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Splicing regulation involves many factors, such as proteins, non-coding RNAs, and DNA sequences at many steps. Thus, the dysregulation of splicing is caused by many factors, including mutations in RNA splicing factors, aberrant expression levels of RNA splicing factors, small nuclear ribonucleoproteins biogenesis, mutations in snRNA, or genomic sequences that are involved in the regulation of splicing, such as 5’ and 3’ splice sites, branch point site, splicing enhancer/silencer, and changes in the chromatin status that affect the splicing profile. This review focuses on the dysregulation of RNA splicing related to cancer and the associated therapeutic methods.

scholarly journals Bound in Hatred: The role of group-based morality in acts of hate

2019 ◽  
Author(s):  
Joseph Hoover ◽  
Mohammad Atari ◽  
Aida Mostafazadeh Davani ◽  
Brendan Kennedy ◽  
Gwenyth Portillo-Wightman ◽  
...  
Keyword(s):  
Language Processing ◽  
Spatial Modeling ◽  
Hate Speech ◽  
Moral Values ◽  
Unified Framework ◽  
Hate Groups ◽  
Marginalized Groups ◽  
Motivated Behaviors ◽  
The Relationship

Acts of hate have been used to silence, terrorize, and erase marginalized social groups throughout history. The rising rates of these behaviors in recent years underscores the importance of developing a better understanding of when, why, and where they occur. In this work, we present a program of research that suggests that acts of hate may often be best understood not just as responses to threat, but also as morally motivated behaviors grounded in people’s moral values and perceptions of moral violations. As evidence for this claim, we present findings from five studies that rely on a combination of natural language processing, spatial modeling, and experimental methods to investigate the relationship between moral values and acts of hate toward marginalized groups. Across these studies, we find consistent evidence that moral values oriented around ingroup preservation are disproportionately evoked in hate speech, predictive of the county-level prevalence of hate groups, and associated with the belief that acts of hate against marginalized groups are justified. Additional analyses suggest that the association between group-oriented moral values and hate acts against marginalized groups can be partly explained by the belief that these groups have done something morally wrong. By accounting for the role of moralization in acts of hate, this work provides a unified framework for understanding hateful behaviors and the events or dynamics that trigger them.

scholarly journals Relationship between bank competition and stability: the case of the UK

2018 ◽  
Vol 13 (1) ◽  
pp. 98-114 ◽  
Author(s):  
Alau Zhanbolatova ◽  
Sayabek Ziyadin ◽  
Kairat Zhumanov ◽  
Almagul Jumabekova
Keyword(s):  
Empirical Studies ◽  
Moderate Level ◽  
Bank Competition ◽  
Unified Framework ◽  
Large Sample ◽  
The Uk ◽  
The Relationship ◽  
Bank Soundness

There is no consensus in theoretical and empirical studies about the relationship between bank competition and stability. This research aims to investigate the relationship between bank competition and stability in the UK. The analysis has been done on a large sample of UK banks for the period 2004–2014. There is quite contrasting evidence on the bank competition and bank soundness relationship. A unified framework has been developed to assess how different factors may make it more likely that the data favor one theory over another. The results suggest that in some cases a U-shaped relationship exists between bank competition and stability. Therefore the conclusion is that in order to protect the bank from different risk exposures a moderate level of bank competition is needed.

scholarly journals Patterns of the aquatic macrophyte cover in Cachoeira Dourada Reservoir (GO-MG)

2005 ◽  
Vol 65 (1) ◽  
pp. 19-24 ◽  
Author(s):  
L. M Bini ◽  
L. G Oliveira ◽  
D. C Souza ◽  
P. Carvalho ◽  
M. P. Pinto
Keyword(s):  
Aquatic Macrophytes ◽  
Positive Relationship ◽  
Aquatic Macrophyte ◽  
Main Body ◽  
Frequency Of Occurrence ◽  
Frequent Species ◽  
Eichhornia Azurea ◽  
The Relationship ◽  
Macrophyte Cover

The relationship between the aquatic macrophyte cover in upper segments of tributaries and this cover in these tributaries but near the reservoir's main body was tested. Sixteen taxa belonging to 12 families of aquatic macrophytes were recorded in Cachoeira Dourada Reservoir. The most frequent species were Eichhornia azurea (frequency of occurrence = 92%; n = 37 sites) and E. crassipes (44%). Upper segments of the tributaries were the main areas colonized by these aquatic macrophytes. The positive relationship between the aquatic macrophyte cover between the upper and lower segments of tributaries indicates the importance of dispersion in the colonization of the arms and the reservoir's main body.

scholarly journals Aberrant RNA Splicing in Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 167-185 ◽  
Author(s):  
Luisa Escobar-Hoyos ◽  
Katherine Knorr ◽  
Omar Abdel-Wahab
Keyword(s):  
Small Molecules ◽  
Rna Splicing ◽  
Clinical Development ◽  
Splicing Factors ◽  
Global Changes ◽  
Splicing Regulation ◽  
Enzymatic Process ◽  
Patients With Cancer ◽  
Aberrant Rna

RNA splicing, the enzymatic process of removing segments of premature RNA to produce mature RNA, is a key mediator of proteome diversity and regulator of gene expression. Increased systematic sequencing of the genome and transcriptome of cancers has identified a variety of means by which RNA splicing is altered in cancer relative to normal cells. These findings, in combination with the discovery of recurrent change-of-function mutations in splicing factors in a variety of cancers, suggest that alterations in splicing are drivers of tumorigenesis. Greater characterization of altered splicing in cancer parallels increasing efforts to pharmacologically perturb splicing and early-phase clinical development of small molecules that disrupt splicing in patients with cancer. Here we review recent studies of global changes in splicing in cancer, splicing regulation of mitogenic pathways critical in cancer transformation, and efforts to therapeutically target splicing in cancer.

Autism Symptom Topography and Maternal Socioemotional Functioning

2010 ◽  
Vol 115 (3) ◽  
pp. 234-249 ◽  
Author(s):  
Naomi Ekas ◽  
Thomas L. Whitman
Keyword(s):  
Social Impact ◽  
Maternal Outcomes ◽  
Frequency Of Occurrence ◽  
Substantial Portion ◽  
Symptom Dimensions ◽  
Socioemotional Functioning ◽  
Autism Symptomatology ◽  
Relationship Of ◽  
The Relationship ◽  
Symptom Type

Abstract Researchers examining the relationship of autism symptomatology and maternal stress have defined symptomatology in terms of level of severity, frequency of occurrence, or symptom type. In the present study, the relationship of maternal perceptions of these dimensions, along with a fourth, symptom diversity, and negative and positive indices of maternal socioemotional functioning was evaluated. Results indicate that each of these symptom dimensions was correlated with most of the measures of negative socioemotional status, together accounting for a substantial portion of the variance in these outcomes. The dimensions were especially robust predictors of negative but not positive maternal outcomes. The need for a systematic multidimensional assessment to evaluate autism symptomatology and its social impact was discussed.

Relationship between abiraterone exposure, prostate-specific antigen (PSA) kinetics, and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) .

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 39-39 ◽  
Author(s):  
Steven Xu ◽  
Charles J. Ryan ◽  
Kim Stuyckens ◽  
Matthew R. Smith ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Specific Antigen ◽  
Maximum Effect ◽  
Castration Resistant Prostate Cancer ◽  
Modeling Framework ◽  
Psa Kinetics ◽  
Castration Resistant ◽  
Survival Modeling ◽  
The Relationship

39 Background: Abiraterone, the active metabolite of abiraterone acetate (AA), is an effective androgen biosynthesis inhibitor for patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted a sequential exposure-biomarker-survival modeling analysis to explore the relationship between prostate-specific antigen (PSA) kinetics and overall survival (OS) and to establish the exposure response for PSA kinetics and OS in chemotherapy-naïve and -pretreated patients with mCRPC following AA administration. Methods: The exposure-PSA-survival modeling framework was based on two phase III studies, COU-AA-301 (chemotherapy-pretreated, N = 1184) and COU-AA-302 (chemotherapy-naïve, N = 1081), and included a mixed-effects tumor growth inhibition (TGI) model to describe PSA dynamics in response to AA and a Cox proportional hazards survival model to evaluate the relationship between relative risk of death and PSA dynamic end points. Results: The TGI model best described the longitudinal PSA dynamics following AA treatment. Abiraterone exposure significantly increased PSA decay rate (maximum effect of 2.72, p < 0.0001). The estimated concentration for 50% of the maximum effect (EC50) was 4.75 ng/mL. The abiraterone effect on PSA kinetics was similar in chemotherapy-naïve and -pretreated subjects, and approximately 90% of subjects had a steady-state concentration greater than the EC50. All model-predicted PSA metrics were strongly associated with OS in both populations; model-based post-treatment PSA doubling time showed the strongest association (hazard ratios approximately 0.9 in both populations). Simulations showed that the modeling framework could accurately predict the survival outcome for both studies. Conclusions: The analysis revealed a similar effect of abiraterone on PSA kinetics and association between PSA kinetics and OS in chemotherapy-naïve and -pretreated subjects, providing additional evidence for surrogacy of PSA kinetics and the use of PSA end points to indicate clinical benefit of abiraterone in subjects with mCRPC regardless of prior chemotherapy. Furthermore, the study confirmed that the recommended 1,000 mg/d dose of AA leads to adequate clinical exposure above the effective level. Clinical trial information: NCT00638690, NCT00887198.

scholarly journals Anthropogenic Decline of African Dust inferred from Insights From the Holocene Records and Beyond: are dust purely  natural?

2021 ◽  
Author(s):  
Tianle Yuan ◽  
Hongbin Yu ◽  
Mian Chin ◽  
Lorraine Remer ◽  
David McGee ◽  
...  
Keyword(s):  
Surface Wind ◽  
Dust Emission ◽  
Surface Wind Speed ◽  
Natural Phenomenon ◽  
Unified Framework ◽  
Dust Source ◽  
The Holocene ◽  
African Dust ◽  
Source Regions ◽  
The Relationship

&lt;p&gt;African dust exhibits strong variability on a range of time scales. Here we show that the interhemispheric contrast in Atlantic SST (ICAS) drives African dust variability at decadal to millennial timescales, and the strong anthropogenic increase of the ICAS in the future will decrease African dust loading to a level never seen during the Holocene. We provide a physical framework to understand the relationship between the ICAS and African dust activity: positive ICAS anomalies push the Intertropical Convergence Zone (ITCZ) northward and decrease surface wind speed over African dust source regions, which reduces dust emission and transport. It provides a unified framework for and is consistent with relationships in the literature. We find strong observational and proxy&amp;#8208;record support for the ICAS&amp;#8208;ITCZ&amp;#8208;dust relationship during the past 160 and 17,000 years. Model&amp;#8208;projected anthropogenic increase of the ICAS will reduce African dust by as much as 60%, which has broad consequences. We posit that dust cannot be thought of as a purely natural phenomenon.&lt;/p&gt;

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