Numerical analysis of weak random drift in a cline

The equilibrium state of a diffusion model for weak random genetic drift in a cline is analyzed numerically. The monoecious organism occupies an unbounded linear habitat with constant, uniform population density. Migration is homogeneous, symmetric, and independent of genotype. A single diallelic locus with a step environment is investigated in the absence of dominance and mutation. The ratio of the variance of either gene frequency to the product of the expected gene frequencies decreases monotonically to a non-zero constant. The correlation between the gene frequencies at two points decreases monotonically to zero as the separation is increased with the average position fixed; the decrease is asymptotically exponential. The correlation decreases monotonically to a positive constant depending on the separation as the average position increasingly deviates from the center of the cline with the separation fixed. The correlation also decreases monotonically to zero if one of the points is fixed and the other is moved outward in the habitat, the ultimate decrease again being exponential. All the results are parameter free. Some asymptotic formulae are derived analytically.     

A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia

BackgroundAlthough cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice.ConclusionsThe IGP model was not completely validated in our cohort. However, mutations in six out of the nine genes can be used to characterize survival (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust prognostication in the patients who are re-categorized by the IGP model. These mutations should be incorporated into clinical testing for younger patients outside of clinical trials, in order to guide therapy.     

The ecology of the banded civet (Hemigalus derbyanus) in Southeast Asia with implications for mesopredator release,zoonotic diseases,and conservation

Habitat loss and degradation threaten forest specialist wildlife species, but some generalist mesopredators exploit disturbed areas and human‐derived food, which brings them into closer contact with humans. Mesopredator release is also important for human health for known zoonotic disease reservoirs, such as Asian civets (Viverridae family), since this group includes the intermediator species for the SARS‐CoV‐1 outbreak. Here we use camera trapping to evaluate the habitat associations of the widespread banded civet (Hemigalus derbyanus) across its range in Southeast Asia. At the regional scale, banded civet detections among published studies were positively associated with forest cover and negatively associated with human population. At the local scale (within a landscape), hierarchical modeling of new camera trapping showed that abundance was negatively associated with forest loss and positively associated with distance to rivers. These results do not support mesopredator release and suggest a low likelihood overlap with humans in degraded habitats and, therefore, a low risk of zoonotic disease transmission from this species in the wild. We also estimate that banded civet distribution has contracted to under 21% of its currently recognized IUCN Red List range, only 12% of which falls within protected areas, and a precipitous recent decline in population size. Accordingly, we suggest the banded civet''s Red List status should be re‐evaluated in light of our findings.     

The progenitor cells of the embryonic telencephalon and the neonatal anterior subventricular zone differentially regulate their cell cycle

For the last 10 years our laboratory has been studying the proliferation, migration and differentiation of neuronal progenitor cells located in the anterior part of the postnatal forebrain subventricular zone (SVZa). SVZa-derived cells possess a number of proliferative characteristics that distinguish them from the other progenitor cells in the central nervous system. This review summarizes our recent findings, in which we compared the pattern of cell cycle inhibitory proteins expressed by the neonatal SVZa to that of telencephalic ventricular zone cells.     

The neuronal progenitor cells of the forebrain subventricular zone: intrinsic properties in vitro and following transplantation

During the development of the central nervous system, progenitor cells, located within distinct germinal zones, produce presumptive neurons that migrate to their destinations and differentiate. Recent studies have demonstrated that a discrete region of the anterior part of the postnatal subventricular zone (SVZa) comprises neuronal progenitor cells whose progeny are fated to become the interneurons of the olfactory bulb. The SVZa is of particular interest because it is one of few germinal zones to persist postnatally and may be the only postnatal germinal zone to give rise exclusively to neurons. To the extent that the SVZa is unique among proliferative zones, the SVZa progeny are unique among neurons. First, unlike most cortical neurons, the SVZa-derived cells do not rely on radial glia-assisted migration when traveling to their target region. Second, the SVZa progeny continue to proliferate as they migrate to their target region. And third, the SVZa progeny express early neuron-specific antigens prior to their final division and, therefore, prior to reaching their destination where they will terminally differentiate. To better understand the capacity of the SVZa progeny to concurrently proliferate, migrate, and differentiate, we studied the cells in vitro and following transplantation into the neonatal SVZa and adult striatum. In each setting, we found that the SVZa cells continue both to proliferate and to differentiate into neurons. In addition, after homotopic and heterotopic transplantation, we found that the SVZa cells maintain their ability to migrate. These results suggest that the unique features of the SVZa progeny are specified intrinsically rather than by their extrinsic environment.     

Immunodominance of the VH1-46 antibody gene segment in the primary repertoire of human rotavirus-specific B cells is reduced in the memory compartment through somatic mutation of nondominant clones

Detailed characterization of Ag-specific naive and memory B cell Ab repertoires elucidates the molecular basis for the generation of Ab diversity and the optimization of Ab structures that bind microbial Ags. In this study, we analyzed the immunophenotype and VH gene repertoire of rotavirus (RV) VP6-specific B cells in three circulating naive or memory B cell subsets (CD19+IgD+CD27-, CD19+IgD+CD27+, or CD19+IgD-CD27+) at the single-cell level. We aimed to investigate the influence of antigenic exposure on the molecular features of the two RV-specific memory B cell subsets. We found an increased frequency of CD19+IgD+CD27+ unclass-switched memory B cells and a low frequency of somatic mutations in CD19+IgD-CD27+ class-switched memory B cells in RV-specific memory B cells, suggesting a reduced frequency of isotype switching and somatic mutation in RV VP6-specific memory B cells compared with other memory B cells. Furthermore, we found that dominance of the VH1-46 gene segment was a prominent feature in the VH gene repertoire of RV VP6-specific naive B cells, but this dominance was reduced in memory B cells. Increased diversity in the VH gene repertoire of the two memory B cell groups derived from broader usage of VH gene segments, increased junctional diversity that was introduced by differential TdT activities, and somatic hypermutation.     

Transforming growth factor-α expands progenitor cells of the basal forebrain,but does not promote cholinergic differentiation

Transforming growth factor-α (TGF-α), a member of the epidermal growth factor (EGF) family, binds to the EGF-receptor (EGF-R). The early expression and widespread distribution of TGF-α and EGF-R in the developing central nervous system (CNS) suggest that TGF-α may play a role in the developing CNS. To study possible effects of TGF-α on cholinergic differentiation in the basal forebrain, we cultured septal nuclei with adjacent basal forebrain from embryonic rat brain in the presence and absence of TGF-α. At the highest dose of TGF-α used (100 ng/mL), activity of choline acetyltransferase (ChAT; EC 2.3.1.6) and the number of cholinergic neurons doubled. However, because protein levels tripled, specific ChAT activity actually declined. To determine the mechanism accounting for the increase in ChAT, we labeled dividing precursors present in the cultures with a replication-deficient retrovirus expressing β-galactosidase in the presence and absence of TGF-α. By staining the cultures for both LacZ and ChAT, we determined that the precursor population expanded in size (individually labeled clones contained more cells), but the percentage of cholinergic neurons present in the clones was unchanged. Therefore, while TGF-α expands the precursor pool, it does not promote cholinergic differentiation. Interleukin-9, included to prompt neuronal differentiation, did not by itself increase ChAT activity, nor did it enhance the action of TGF-α. This was true even when basic fibroblast growth factor was included. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 405–412, 1998     

Modern Hunting Practices and Wild Meat Trade in the Oil Palm Plantation-Dominated Landscapes of Sumatra,Indonesia

The ongoing expansion of plantation agriculture has changed the ecological, demographic, and social conditions of Southeast Asia’s forested areas, yet little is known about hunting practices in these novel landscapes. Using information from 73 in-depth interviews with hunters, agricultural workers and wild meat dealers in the Jambi province of Sumatra, Indonesia, we describe contemporary hunting practices, including how hunting methods, wildlife harvest and consumption rates vary between different indigenous and immigrant ethnic groups. Hunting is now primarily a commercial endeavor for harvesting wild boar (Sus scrofa) meat; over 7500 wild boars were sold in Jambi City alone in 2011. The Muslim majority avoids wild boar for religious reasons, but there is substantial local and export demand driven by Chinese and Christian Batak. We conclude that hunting within oil palm plantations may reduce crop damage from wild boar and also yield large amounts of wild meat with relatively little by-catch of threatened animals.     

Burial of nonpolar surface area and thermodynamic stabilization of globins as a function of chain elongation

Proteins are biosynthesized from N to C terminus before they depart from the ribosome and reach their bioactive state in the cell. At present, very little is known about the evolution of conformation and the free energy of the nascent protein with chain elongation. These parameters critically affect the extent of folding during ribosome‐assisted biosynthesis. Here, we address the impact of vectorial amino acid addition on the burial of nonpolar surface area and on the free energy of native‐like structure formation in the absence of the ribosomal machinery. We focus on computational predictions on proteins bearing the globin fold, which is known to encompass the 3/3, 2/2, and archaeal subclasses. We find that the burial of nonpolar surface increases progressively with chain elongation, leading to native‐like conformations upon addition of the last C‐terminal residues, corresponding to incorporation of the last two helices. Additionally, the predicted folding entropy for generating native‐like structures becomes less unfavorable at nearly complete chain lengths, suggesting a link between the late burial of nonpolar surface and water release. Finally, the predicted folding free energy takes a progressive favorable dip toward more negative values, as the chain gets longer. These results suggest that thermodynamic stabilization of the native structure of newly synthesized globins during translation in the cell is significantly enhanced as the chain elongates. This is especially true upon departure of the last C‐terminal residues from the ribosomal tunnel, which hosts ca., 30–40 amino acids. Hence, we propose that release from the ribosome is a crucial step in the life of single‐domain proteins in the cell. Proteins 2014; 82:2318–2331. © 2014 Wiley Periodicals, Inc.     

Rate and pattern of migration of lineally-related olfactory bulb interneurons generated postnatally in the subventricular zone of the rat

A spatially discrete region of the anterior part of the postnataltelescephalic subventricular zone, referred to as the SVZa generatesvast numbers of lineally-related neurons destined for the olfactorybulb (Luskin, 1993). The cells originating in the SVZa migrateto the olfactory bulb along a highly restricted pathway whichis in a direction orthogonal to the orientation of radial glialfibers. In this study we analysed the number, distribution,orientation and rate of migration of SVZa-derived cells as theyapproach the olfactory bulb. In order to track the SVZa-derivedcells, a retroviral lineage tracer, encoding the reporter geneE.coli ß-galactosidase (lacZ) was injected preciselyinto the rat SVZa at postnatal day 1 (Pl). The lacZ-positivecells were visualized 1, 2 and 3 days later by X-Gal histochemistryin cryostat sections. As the number of SVZa-derived cells inthe pathway increased with survival time, their distributionchanged systematically. The distribution pattern of lacZ-positivecells by 2 and 3 days postinjection suggested that some of theprogeny of infected progenitor cells were undergoing neurogenesisas they proceeded to the olfactory bulb; a large percentageof the lacZ-positive cells were substantially displaced fromthe SVZa injection site. To investigate whether lacZ-positivecells migrate in a directed fashion, their orientation preferencewas scored. For the majority of lacZ-positive cells (>94%),their leading process was directed toward the olfactory bulb,possibly reflecting a response to migratory cues present alongthe pathway. The estimated average rate of cell migration tothe olfactory bulb was 23 µm/h, which is approximatelytwice the speed of radially directed neuronal migration fromthe telencephalic ventricular zone to the cortical plate (O'Rourkeet al, 1992). Collectively, these results suggest that SVZa-derivedintemeurons en route to the olfactory bulb may employ a novelmode of tangential migration.