Sociocognitive and socioemotive factors associated with early academic abilities in preschool children in Costa Rica

This study aims at providing a multi-report, multi-method model of academic and socio-emotional preparation in preschool children that integrates bodies of previous research that have been conducted primarily in isolation. The main purpose is to test a comprehensive model of self-regulation and its links to moral reasoning, prosocial behaviors and early academic abilities. Participants were 193 Costa Rican preschool children for whom parent- and teacher- reports were collected. Also, children were evaluated with performance tests. The results showed that self-regulation is better represented as a bifactorial model with both cognitive and emotional components. Also, the study showed evidence suggesting that prosocial behaviors in preschoolers are better explained as a multidimensional construct rather than a unidimensional variable. Cognitive self-regulation showed positive links with prosocial moral reasoning, prosocial behaviors and early academic abilities, whereas emotion regulation showed only significant relations with prosocial behaviors. The relations between self-regulation and early academic abilities were direct and not mediated by prosocial moral reasoning or prosocial behaviors. The results are discussed in light of previous findings, and some implications for theories of human development and future interventions are presented

The architecture of the BubR1 tetratricopeptide tandem repeat defines a protein motif underlying mitotic checkpoint-kinetochore communication

The accurate and timely transmission of the genetic material to progeny during successive rounds of cell division is sine qua non for the maintenance of genome stability. Eukaryotic cells have evolved a surveillance mechanism, the mitotic spindle assembly checkpoint (SAC), to prevent premature advance to anaphase before every chromosome is properly attached to microtubules of the mitotic spindle. The architecture of the KNL1-BubR1 complex reveals important features of the molecular recognition between SAC components and the kinetochore. The interaction is important for a functional SAC as substitution of BubR1 residues engaged in KNL1 binding impaired the SAC and BubR1 recruitment into checkpoint complexes in stable cell lines. Here we discuss the implications of the disorder-to-order transition of KNL1 upon BubR1 binding for SAC signaling and propose a mechanistic model of how BUBs binding may affect the recognition of KNL1 by its other interacting partners

Shell Utilization Pattern by the Hermit Crab Isocheles sawayai Forest and Saint Laurent, 1968 (Anomura, Diogenidae) from Margarita Island, Caribbean Sea, Venezuela

Isocheles sawayai is a hermit crab that is occasionally mentioned in the literature, and recently its distribution was extended to Venezuelan waters. Because no information on the biology and shell use patterns of this species inhabiting Caribbean waters is available, we provide the first information on shell occupation patterns of I. sawayai from Venezuela. Specimens were collected monthly from January to December 2000 along the sandy shore of Margarita Island, Venezuela. The 942 specimens collected showed different shell use patterns between the sexes and according to the reproductive condition of the females. The gastropods Leucozonia nassa (37.37%), Engoniophos unicinctus (25.37%), Nassarius vibex (4.88%), Melongena melongena (4.25%), and Stramonita haemastoma (3.82%) represent 76% of the total occupied shells. Of the total of 26 different shell species occupied by I. sawayai, males were found occupying 21, while females were found occupying all 26 shell species. In general, both sexes most frequently occupied L. nassa and E. unicinctus. However, the percentage of females occupying these shells was significantly higher than that of the males. Regression analyses showed the best correlation between crab size, shell aperture width, and shell internal volume. The current comparative investigation, in combination with other South Atlantic populations of I. sawayai, provided further evidence of shell use adaptation in hermit crabs from different areas, and increases our insight into shell use of shallow-water hermit crabs

High resolution HLA-A, -B, -C and -DRB1 allele and haplotype frequencies in the Costa Rica Central Valley population

The Costa Rica Central Valley population (CCVP) is the major population in this country, accounting for over 60% of the Costa Rican inhabitants concentrated since colonial times in a 2,500 km2 intermontane region. Interesting historic, demographic and genetic characteristics of this hybrid population have attracted researchers interested in testing genetic associations for various diseases. However, no study describing Human Leukocyte Antigen (HLA) frequencies by molecular methods had been performed. We have recently described low resolution HLA allele group and haplotype frequencies in a sample of this population. In this report, we extend our study to high resolution by sequence-based typing of exons 2, 3 and 4 for class I, and exon 2 for HLA-DRB1. DNA was extracted from blood or saliva samples from a cohort of 205 non-related healthy donors recruited as part of the University of Costa Rica’s Centre for Research in Hematology and Related Disorders (CIHATA) DNA bank. All participants were born in the CCVP and gave informed consent. A total of 37 HLA-A, 61 HLA-B, 24 HLA-C and 38 HLA-DRB1 alleles were seen in this sample. The five most frequent alleles for these genes are HLA-A*02:01:01, HLA-A*24:02:01, HLA-A*03:01:01, HLA-A*01:01:01, HLA-A*68:01:02, HLA-B*07:02:01, HLA-B*40:02:01, HLA-B*35:01:01, HLA-B*44:02:01, HLA-B*14:02:01, HLA-C*04:01:01, HLA-C*07:02:01, HLA-C*03:05, HLA-C*06:02:01, HLA-C*07:01:01, HLA-DRB1*13:01:01G, HLA-DRB1*04:07:01G, HLA-DRB1*15:01:01G, HLA-DRB1*03:01:01G, and HLA-DRB1*07:01:01G. Preliminary haplotype estimation results show, as a proxy for admixture proportions, that 68% of the extended haplotypes are Caucasian, while 23% are Amerindian in origin and 9% are clearly Sub-Saharan African. Principal coordinates analysis based on HLA-A and –B allele group frequencies reveals that this population clusters among other admixed groups with strong Caucasian component that lie closely to Iberian populations

Defining the molecular basis of BubR1 kinetochore interactions and APC/C-CDC20 inhibition.

BubR1 is essential for the mitotic checkpoint that prevents aneuploidy in cellular progeny by triggering anaphase delay in response to kinetochores incorrectly/not attached to the mitotic spindle. Here, we define the molecular architecture of the functionally significant N-terminal region of human BubR1 and present the 1.8 A crystal structure of its tetratricopeptide repeat (TPR) domain. The structure reveals divergence from the classical TPR fold and is highly similar to the TPR domain of budding yeast Bub1. Shared distinctive features include a disordered loop insertion, a 3(10)-helix, a tight turn involving glycine positive Phi angles, and noncanonical packing of and between the TPR motifs. We also define the molecular determinants of the interaction between BubR1 and kinetochore protein Blinkin. We identify a shallow groove on the concave surface of the BubR1 TPR domain that forms multiple discrete and potentially cooperative interactions with Blinkin. Finally, we present evidence for a direct interaction between BubR1 and Bub1 mediated by regions C-terminal to their TPR domains. This interaction provides a mechanism for Bub1-dependent kinetochore recruitment of BubR1. We thus present novel molecular insights into the structure of BubR1 and its interactions at the kinetochore-microtubule interface. Our studies pave the way for future structure-directed engineering aimed at dissecting the roles of kinetochore-bound and other pools of BubR1 in vivo

Deregulation of chromosome segregation and cancer

The mitotic spindle assembly checkpoint (SAC) is an intricate cell signaling system that ensures the high fidelity and timely segregation of chromosomes during cell division. Mistakes in this process can lead to the loss, gain, or rearrangement of the genetic material. Gross chromosomal aberrations are usually lethal but can cause birth and development defects as well as cancer. Despite advances in the identification of SAC protein components, important details of the interactions underpinning chromosome segregation regulation remain to be established. This review discusses the current understanding of the function, structure, mode of regulation, and dynamics of the assembly and disassembly of SAC subcomplexes, which ultimately safeguard the accurate transmission of a stable genome to descendants. We also discuss how diverse oncoviruses take control of human cell division by exploiting the SAC and the potential of this signaling circuitry as a pool of drug targets to develop effective cancer therapies

Interfering with mRNA methylation by the 2′O-Methyltransferase (NSP16) from SARS-CoV-2 to tackle the COVID-19 disease

The pandemic associated to Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) has resulted in a huge number of deaths and infected people. Although several vaccine programmes are currently underway and have reached phase 3, and a few small size drugs repurposed to aid treatment of severe cases of COVID-19 infections, effective therapeutic options for this disease do not currently exist. NSP16 is a S-adenosyl-L-Methionine (SAM) dependent 2′O-Methyltransferase that converts mRNA cap-0 into cap-1 structure to prevent virus detection by cell innate immunity mechanisms. NSP16 methylates the ribose 2′O-position of the first nucleotide of the mRNA only in the presence of an interacting partner, the protein NSP10. This feature suggests that inhibition of the NSP16 may represent a therapeutic window to treat COVID-19. To test this idea, we performed comparative structural analyses of the NSP16 present in human coronaviruses and developed a sinefungin (SFG) similarity-based virtual screening campaign to assess the druggability of the SARS-CoV-2 NSP16 enzyme. Through these studies, we identified the SFG analogue 44601604 as a promising more potent inhibitor of NSP16 to limit viral replication in infected cells, favouring viral clearance

Structural insights into the role of domain flexibility in human DNA ligase IV.

Knowledge of the architecture of DNA ligase IV (LigIV) and interactions with XRCC4 and XLF-Cernunnos is necessary for understanding its role in the ligation of double-strand breaks during nonhomologous end joining. Here we report the structure of a subdomain of the nucleotidyltrasferase domain of human LigIV and provide insights into the residues associated with LIG4 syndrome. We use this structural information together with the known structures of the BRCT/XRCC4 complex and those of LigIV orthologs to interpret small-angle X-ray scattering of LigIV in complex with XRCC4 and size exclusion chromatography of LigIV, XRCC4, and XLF-Cernunnos. Our results suggest that the flexibility of the catalytic region is limited in a manner that affects the formation of the LigIV/XRCC4/XLF-Cernunnos complex

Effects of fungicide application timing and cultivar resistance on Fusarium head blight and deoxynivalenol in winter wheat

Fusarium graminearum causes Fusarium head blight (FHB) in wheat. FHB reduces yield and quality and contaminates grain with the mycotoxin deoxynivalenol (DON). Effective management strategies are needed. The objectives of this research were to 1) Determine the effect of fungicide application timing at anthesis (the standard timing) and 6 and 12 days later on FHB and DON in the winter wheat cultivars Overley (susceptible) and Overland (moderately resistant) and 2) Compare the effects of a triazole and a strobilurin fungicide on FHB and DON in Overley and Overland. In 2015 two field trials (irrigated and rain-fed) were conducted in Nebraska, USA. The triazole Prosaro (prothioconazole + tebuconazole) and the strobilurin Headline (pyraclostrobin) were applied with a CO2-powered backpack sprayer at anthesis and 6 and 12 days later. A split plot design in randomized complete blocks with 4 replications was used. Main plots were cultivars and subplots were fungicide treatments. FHB index and DON were significantly (P \u3c 0.05) lower in Overland than in Overley. The window of fungicide application to control FHB and DON was widened from anthesis to 6 days later without loss of efficacy. Headline was less effective than Prosaro in controlling FHB and DON. Moderate resistance combined with a triazole fungicide most effectively reduced FHB and DON. The results indicate a wider fungicide application window and the effectiveness of combining resistance with a triazole fungicide