Reconstructing the last common ancestor of all eukaryotes.

Understanding the origin of eukaryotic cells is one of the most difficult problems in all of biology. A key challenge relevant to the question of eukaryogenesis is reconstructing the gene repertoire of the last eukaryotic common ancestor (LECA). As data sets grow, sketching an accurate genomics-informed picture of early eukaryotic cellular complexity requires provision of analytical resources and a commitment to data sharing.

The emerging view on the origin and early evolution of eukaryotic cells.

The origin of the eukaryotic cell, with its compartmentalized nature and generally large size compared with bacterial and archaeal cells, represents a cornerstone event in the evolution of complex life on Earth. In a process referred to as eukaryogenesis, the eukaryotic cell is believed to have evolved between approximately 1.8 and 2.

Kinetoplastid kinetochore proteins KKT14-KKT15 are divergent Bub1/BubR1-Bub3 proteins.

Faithful transmission of genetic material is crucial for the survival of all organisms. In many eukaryotes, a feedback control mechanism called the spindle checkpoint ensures chromosome segregation fidelity by delaying cell cycle progression until all chromosomes achieve proper attachment to the mitotic spindle. Kinetochores are the macromolecular complexes that act as the interface between chromosomes and spindle microtubules.

Desensitized gamers? Violent video game exposure and empathy for pain in adolescents - an ERP study.

This Event-Related Potential (ERP) study aimed to test how habitual and short-term violent video game exposure (VVGE) may affect empathy for pain responses in adolescents. In a within-subjects design, boys ( = 56; aged 12-16 years) performed a pain judgment task before and immediately after playing a violent video game. In this task, participants judged whether photos of hands depicted on their screen were in a painful situation or not.

Towards unraveling the origins of eukaryotic nuclear genome organization.

With 3D genome mapping maturing over the past decade, studies exposed the differences between eukaryotic and prokaryotic genome organization. This raises the question of how the complex eukaryotic genome organization originated. Here, I explore potential pathways to answering this question, guided by our changing understanding of the origins of eukaryotes.

Increased Sampling and Intracomplex Homologies Favor Vertical Over Horizontal Inheritance of the Dam1 Complex.

Kinetochores connect chromosomes to spindle microtubules to ensure their correct segregation during cell division. Kinetochores of human and yeasts are largely homologous, their ability to track depolymerizing microtubules, however, is carried out by the nonhomologous complexes Ska1-C and Dam1-C, respectively. We previously reported the unique anti-correlating phylogenetic profiles of Dam1-C and Ska-C found among a wide variety of eukaryotes.

Chromosomal instability by mutations in the novel minor spliceosome component CENATAC.

Aneuploidy is the leading cause of miscarriage and congenital birth defects, and a hallmark of cancer. Despite this strong association with human disease, the genetic causes of aneuploidy remain largely unknown. Through exome sequencing of patients with constitutional mosaic aneuploidy, we identified biallelic truncating mutations in CENATAC (CCDC84).

Molecular characterization of the conoid complex in Toxoplasma reveals its conservation in all apicomplexans, including Plasmodium species.

The apical complex is the instrument of invasion used by apicomplexan parasites, and the conoid is a conspicuous feature of this apparatus found throughout this phylum. The conoid, however, is believed to be heavily reduced or missing from Plasmodium species and other members of the class Aconoidasida. Relatively few conoid proteins have previously been identified, making it difficult to address how conserved this feature is throughout the phylum, and whether it is genuinely missing from some major groups.

Timing the origin of eukaryotic cellular complexity with ancient duplications.

Eukaryogenesis is one of the most enigmatic evolutionary transitions, during which simple prokaryotic cells gave rise to complex eukaryotic cells. While evolutionary intermediates are lacking, gene duplications provide information on the order of events by which eukaryotes originated. Here we use a phylogenomics approach to reconstruct successive steps during eukaryogenesis.

Influence of CYP3A5 Genetic Polymorphism on Long-Term Renal Function in Chinese Kidney Transplant Recipients Using Limited Sampling Strategy and Abbreviated Area Under the Curve for Tacrolimus Monitoring.

Introduction: Although the association between CYP3A5 gene polymorphism and tacrolimus dosing requirements was well established, the impact on how CYP3A5 genotype affects the acute rejection and long-term renal function in patients who received kidney transplants and were treated with tacrolimus remained controversial.

Design: Sixty-seven Chinese patients with kidney transplants receiving de novo tacrolimus-based immunosuppressive therapy with known CYP3A5 genotype were divided into 2 groups. Those with at least 1 CYP3A5*1 allele were CYP3A5 expressers while homozygotes for the mutant allele CYP3A5*3 were nonexpressers.

Author Correction: A structural model for microtubule minus-end recognition and protection by CAMSAP proteins.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

"This Is Me, This Is What I Am, I Am a Man": The Masculinities of Men Who Pay for Sex with Women.

This paper draws on theories of masculinity to explore men's motivations for beginning and continuing to pay for sex with women. Based on in-depth interviews with 35 male clients of female sex workers in the UK during 2007/2008, our findings suggest that a desire to pay for sex is often entrenched in notions of hegemonic masculinity such as sex as a drive, or need for a variety of experiences and partners and is rationalized as an economic exchange. Yet, the men interviewed also expressed a need for intimacy, female friendship and conversation in a controlled environment, which challenged dominant masculine ideals.

Impact of CYP3A5 Genetic Polymorphism on Intrapatient Variability of Tacrolimus Exposure in Chinese Kidney Transplant Recipients.

Background: Although high tacrolimus (FK) intrapatient variability (IPV) was shown to be associated with poor graft outcome in kidney transplant recipients (KTRs), it is uncertain whether there is any association between the CYP3A5 genotype and IPV of FK concentrations. Instead of trough level, we use calculated abbreviated AUC to investigate the impact of CYP3A5 genetic polymorphism on IPV of FK pharmacokinetics.

Methods: We conducted a retrospective, single-center study of 86 adult Chinese KTRs with known CYP3A5 genotype.

Mosaic origin of the eukaryotic kinetochore.

The emergence of eukaryotes from ancient prokaryotic lineages embodied a remarkable increase in cellular complexity. While prokaryotes operate simple systems to connect DNA to the segregation machinery during cell division, eukaryotes use a highly complex protein assembly known as the kinetochore. Although conceptually similar, prokaryotic segregation systems and the eukaryotic kinetochore are not homologous.

Inferring the Evolutionary History of Your Favorite Protein: A Guide for Molecular Biologists.

Comparative genomics has proven a fruitful approach to acquire many functional and evolutionary insights into core cellular processes. Here it is argued that in order to perform accurate and interesting comparative genomics, one first and foremost has to be able to recognize, postulate, and revise different evolutionary scenarios. After all, these studies lack a simple protocol, due to different proteins having different evolutionary dynamics and demanding different approaches.

A structural model for microtubule minus-end recognition and protection by CAMSAP proteins.

CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize noncentrosomal microtubule networks, which are essential for cell division, polarization and differentiation. Here, we found that the CAMSAP C-terminal CKK domain is widely present among eukaryotes and autonomously recognizes microtubule minus ends. Through a combination of structural approaches, we uncovered how mammalian CKK binds between two tubulin dimers at the interprotofilament interface on the outer microtubule surface.

No evidence for progressive deterioration in stimulated insulin secretion in renal transplant recipients after 12years tacrolimus exposure.

Aims: Tacrolimus (Tac) inhibits insulin secretion in a Tac-trough blood level dependent way early post-transplant in renal transplant recipients (Rtx). It is unknown whether long-term exposure results into a progressive beta cells dysfunction.

Methods: Two independent cohorts of Tac-treated non-diabetic Rtx, previously participating in glucose metabolism studies using intravenous Glucose Tolerance Test (ivGTT) were included: Fifty-eight Rtx were tested by ivGTT cross-sectional between 0.

Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics.

During eukaryotic cell division, the sister chromatids of duplicated chromosomes are pulled apart by microtubules, which connect via kinetochores. The kinetochore is a multiprotein structure that links centromeres to microtubules, and that emits molecular signals in order to safeguard the equal distribution of duplicated chromosomes over daughter cells. Although microtubule-mediated chromosome segregation is evolutionary conserved, kinetochore compositions seem to have diverged.

Unique Phylogenetic Distributions of the Ska and Dam1 Complexes Support Functional Analogy and Suggest Multiple Parallel Displacements of Ska by Dam1.

Faithful chromosome segregation relies on kinetochores, the large protein complexes that connect chromatin to spindle microtubules. Although human and yeast kinetochores are largely homologous, they track microtubules with the unrelated protein complexes Ska (Ska-C, human) and Dam1 (Dam1-C, yeast). We here uncovered that Ska-C and Dam1-C are both widespread among eukaryotes, but in an exceptionally inverse manner, supporting their functional analogy.

Effect of Breakfast on the Exposure of the Once-Daily Tacrolimus Formulation in Stable Kidney Transplant Recipients.

Background: The once-daily Tacrolimus formulation (Tac ONCE-DAILY) has to be taken on an empty stomach. This is inconvenient for patients and may hamper compliance. The influence of food intake on the exposure of Tac ONCE-DAILY is unknown in transplant recipients.

Emerging models for facilitating contact between people genetically related through donor conception: a preliminary analysis and discussion.

Previous research indicates interest among some donor-conceived people, donors and recipient parents in having contact. Outcomes of such contact appear largely, but not universally, positive. This paper seeks to understand better the characteristics of associated support services.

Captive chimpanzee takes down a drone: tool use toward a flying object.

On 10 April 2015, a Dutch TV crew was filming at the Royal Burgers Zoo in Arnhem, The Netherlands. It was the intention to film the chimpanzees in the enclosure from close-by and from above with the means of a drone. When the drone came a bit closer to the chimpanzees, a female individual made two sweeps with a branch that she held in one hand.

Disgust-specific modulation of early attention processes.

Although threatening images are known to attract and keep our attention, little is known about the existence of emotion-specific attention effects. In this study (N=46), characteristics of an anticipated, disgust-specific effect were investigated by means of a covert orienting paradigm incorporating pictures that were either disgust-evoking, fear-evoking, happiness-evoking or neutral. Attention adhesion to these pictures was measured by the time necessary to identify a peripheral target, presented 100, 200, 500, or 800 ms after picture onset.

Small homologous blocks in phytophthora genomes do not point to an ancient whole-genome duplication.

Genomes of the plant-pathogenic genus Phytophthora are characterized by small duplicated blocks consisting of two consecutive genes (2HOM blocks) and by an elevated abundance of similarly aged gene duplicates. Both properties, in particular the presence of 2HOM blocks, have been attributed to a whole-genome duplication (WGD) at the last common ancestor of Phytophthora. However, large intraspecies synteny-compelling evidence for a WGD-has not been detected.

Lower variability in 24-hour exposure during once-daily compared to twice-daily tacrolimus formulation in kidney transplantation.

Introduction: Tacrolimus has originally been registered as a twice-daily formulation (Prograf, Tac BID), although a once-daily formulation (Advagraf, Tac QD) is also available. A reduced intrapatient variability of Tac Cmin, a surrogate marker for 24-hour drug exposure (AUC0-24), has been suggested. The variability of AUC0-24 has never been studied prospectively yet.