Leishmania sexual reproductive strategies as resolved through computational methods designed for aneuploid genomes

A cryptic sexual reproductive cycle i

The Disunity of Consciousness

It is commonplace for both philosophers and cognitive scientists to express their allegiance to the "unity of consciousness". This is the claim that a subject’s phenomenal consciousness, at any one moment in time, is a single thing. This view has had a major influence on computational theories of consciousness. In particular, what we call single-track theories dominate the literature, theories which contend that our conscious experience is the result of a single consciousness-making process or mechanism in the brain. We argue that the orthodox view is quite wrong: phenomenal experience is not a unity, in the sense of being a single thing at each instant. It is a multiplicity, an aggregate of phenomenal elements, each of which is the product of a distinct consciousness-making mechanism in the brain. Consequently, cognitive science is in need of a multi-track theory of consciousness; a computational model that acknowledges both the manifold nature of experience, and its distributed neural basis

Contributions of the VitisGen2 project to grapevine breeding and genetics

The VitisGen projects (2011-2022) have improved the tools available for breeding new grapevine cultivars with regional adaptation, high quality, and disease resistance. VitisGen2 (the second project in the series) was a multi-state collaboration (USDA-Geneva, New York; University of California, Davis; USDA-Parlier, California; Cornell University; Missouri State University; University of Minnesota; South Dakota State University; Washington State University; North Dakota State University; and E&J Gallo, California) to develop improved genetic mapping technology; to identify useful DNA marker-trait associations; and to incorporate marker-assisted selection (MAS) into breeding programs. A novel genetic mapping platform (rhAmpSeq) now provides 2000 + markers that are transferable across the Vitis genus. rhAmpSeq has been used in California, New York, Missouri, and South Dakota to identify new QTL for powdery and downy mildew resistance. In addition, fruit/flower traits that would normally take years to phenotype have been associated with predictive markers accessible from seedling DNA (e.g. malate metabolism, anthocyanin acylation, bloom phenology and flower sex). Since 2011, the project has used MAS to screen thousands of grape seedlings from public breeding programs in the United States and has produced “Ren- Stack” public domain lines to enable simultaneous access to 4 or 6 powdery mildew resistance loci from single source genotypes. High-throughput phenotyping for powdery and downy mildew resistance has been revolutionized with the Blackbird automated-imaging system powered by artificial intelligence for image analysis. Affordable DNA sequencing along with phenotyping innovations are transforming grapevine breeding

Gene expression in Leishmania is regulated predominantly by gene dosage

ABSTRACT Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal “somy” (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection. IMPORTANCE Leishmania is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in Leishmania tropica is that of gene dosage at the level of individual genes or chromosomal somy

Quasiparticle spectrum of the cuprate BiSrCaCuO: Possible connection to the phase diagram

We previously introduced [T. Cren et al., Europhys. Lett. 52, 203 (2000)] an energy-dependant gap function, $\Delta(E)$, that fits the unusual shape of the quasiparticle (QP) spectrum for both BiSrCaCuO and YBaCuO. A simple anti-resonance in $\Delta(E)$ accounts for the pronounced QP peaks in the density of states, at an energy $\Delta_p$, and the dip feature at a higher energy, $E_{dip}$. Here we go a step further : our gap function is consistent with the ($T, p$) phase diagram, where $p$ is the carrier density. For large QP energies ($E >> \Delta_p$), the total spectral gap is $\Delta(E) \simeq \Delta_p + \Delta_\phi$, where $\Delta_\phi$ is tied to the condensation energy. From the available data, a simple $p$-dependance of $\Delta_p$ and $\Delta_\phi$ is found, in particular $\Delta_\phi(p) \simeq 2.3 k_B T_c(p)$. These two distinct energy scales of the superconducting state are interpreted by comparing with the normal and pseudogap states. The various forms of the QP density of states, as well as the spectral function $A(k,E)$, are discussed

The interaction of lean and building information modeling in construction

Lean construction and Building Information Modeling are quite different initiatives, but both are having profound impacts on the construction industry. A rigorous analysis of the myriad specific interactions between them indicates that a synergy exists which, if properly understood in theoretical terms, can be exploited to improve construction processes beyond the degree to which it might be improved by application of either of these paradigms independently. Using a matrix that juxtaposes BIM functionalities with prescriptive lean construction principles, fifty-six interactions have been identified, all but four of which represent constructive interaction. Although evidence for the majority of these has been found, the matrix is not considered complete, but rather a framework for research to explore the degree of validity of the interactions. Construction executives, managers, designers and developers of IT systems for construction can also benefit from the framework as an aid to recognizing the potential synergies when planning their lean and BIM adoption strategies

Skin, Thermal and Umbilical Cord Care Practices for Neonates in Southern, Rural Zambia: A Qualitative Study

Background: In Choma District, southern Zambia, the neonatal mortality rate is approximately 40 per 1000 live births and, although the rate is decreasing, many deliveries take place outside of formal facilities. Understanding local practices during the postnatal period is essential for optimizing newborn care programs. Methods: We conducted 36 in-depth interviews, five focus groups and eight observational sessions with recently-delivered women, traditional birth attendants, and clinic and hospital staff from three sites, focusing on skin, thermal and cord care practices for newborns in the home. Results: Newborns were generally kept warm by application of hats and layers of clothing. While thermal protection is provided for preterm and small newborns, the practice of nighttime bathing with cold water was common. The vernix was considered important for the preterm newborn but dangerous for HIV-exposed infants. Mothers applied various substances to the skin and umbilical cord, with special practices for preterm infants. Applied substances included petroleum jelly, commercial baby lotion, cooking oil and breastmilk. The most common substances applied to the umbilical cord were powders made of roots, burnt gourds or ash. To ward off malevolent spirits, similar powders were reportedly placed directly into dermal incisions, especially in ill children. Conclusions: Thermal care for newborns is commonly practiced but co-exists with harmful practices. Locally appropriate behavior change interventions should aim to promote chlorhexidine in place of commonly-reported application of harmful substances to the skin and umbilical cord, reduce bathing of newborns at night, and address the immediate bathing of HIV-infected newborns

Population changes in Leishmania chagasi promastigote developmental stages due to serial passage

Leishmania chagasi causes visceral leishmaniasis, a potentially fatal disease of humans. Within the sand fly vector, L. chagasi replicates as promastigotes which undergo complex changes in morphology as they progress from early stage procyclic promastigotes, to intermediate stage leptomonad and nectomonad promastigotes, and ultimately to terminal stage metacyclic promastigotes that are highly infective to vertebrates. This developmental progression is largely recapitulated in vitro using axenic promastigote cultures that have been passaged only a few times. Within a single passage (which takes about a week), axenic cultures progress from logarithmic to stationary growth phases; parasites within those growth phases progress from stages that do not have metacyclic cell properties to ones that do. Interestingly, repeated serial passage of promastigote cultures will result in cell populations that exhibit perturbations in developmental progression, in expression levels of surface macromolecules (major surface protease, MSP, and promastigote surface antigen, PSA), and in virulence properties, including resistance to serum lysis. Experiments were performed to determine whether there exists a direct relationship between promastigote developmental form and perturbations associated with repeated serial passage. Passage 2 to passage 4 L. chagasi cultures at stationary growth phase were predominately (\u3e85%) comprised of metacyclic promastigotes and exhibited high resistance to serum lysis and high levels of MSP and PSA. Serial passaging 8, or more, times resulted in a stationary phase population that was largely (\u3e85%) comprised of nectomonad promastigotes, almost completely devoid (\u3c2%) of metacyclic promastigotes, and that exhibited low resistance to serum lysis and low levels of MSP and PSA. The study suggests that the loss of particular cell properties seen in cells from serially passaged cultures is principally due to a dramatic reduction in the proportion of metacyclic promastigotes. Additionally, the study suggests that serially passaged cultures may be a highly enriched source of nectomonad-stage promastigotes, a stage that has largely been characterized only in mixtures containing other promastigote forms