Simple guide to starting a research group

Conducting cutting-edge research and scholarship becomes more complicated with each passing year; forming a collaborative research group offers a way to navigate this increasing complexity. Yet many individuals whose work might benefit from the formation of a collaborative team may feel overwhelmed by the prospect of attempting to build and maintain a research group. We propose this simple guide for starting and maintaining such an enterprise

Exceptional skull of huayqueriana (mammalia, litopterna, macraucheniidae) from the late miocene of Argentina: Anatomy, systematics, and peleobiological implications

The Huayquerías Formation (Late Miocene, Huayquerian SALMA) is broadly exposed in westcentral Argentina (Mendoza). The target of several major paleontological expeditions in the first half of the 20th century, the Mendozan Huayquerías (badlands) have recently yielded a significant number of new fossil finds. In this contribution we describe a complete skull (IANIGLA-PV 29) and place it systematically as Huayqueriana cf. H. cristata (Rovereto, 1914) (Litopterna, Macraucheniidae). The specimen shares some nonexclusive features with H. cristata (similar size, rostral border of the orbit almost level with distal border of M3, convergence of maxillary bones at the level of the P3/P4 embrasure, flat snout, very protruding orbits, round outline of premaxillary area in palatal view, and small diastemata between I3/C and C/P1). Other differences (e.g., lack of sagittal crest) may or may not represent intraspecific variation. In addition to other features described here, endocast reconstruction utilizing computer tomography (CT) revealed the presence of a derived position of the orbitotemporal canal running below the rhinal fissure along the lateroventral aspect of the piriform lobe. CT scanning also established that the maxillary nerve (CN V2) leaves the skull through the sphenoorbital fissure, as in all other litopterns, a point previously contested for macraucheniids. The angle between the lateral semicircular canal and the plane of the base of the skull is about 26°, indicating that in life the head was oriented much as in modern horses. Depending on the variables used, estimates of the body mass of IANIGLA-PV 29 produced somewhat conflicting results. Our preferred body mass estimate is 250 kg, based on the centroid size of 36 3D cranial landmarks and accompanying low prediction error. The advanced degree of tooth wear in IANIGLA-PV 29 implies that the individual died well into old age. However, a count of cementum lines on the sectioned left M2 is consistent with an age at death of 10 or 11 years, younger than expected given its body mass. This suggests that the animal had a very abrasive diet. Phylogenetic analysis failed to resolve the position of IANIGLA-PV 29 satisfactorily, a result possibly influenced by intraspecific variation. There is no decisive evidence for the proposition that Huayqueriana, or any other litoptern, were foregut fermenters.Fil: Forasiepi, Analia Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: MacPhee, Ross D. E.. American Museum Of Natural History; Estados UnidosFil: Hernández del Pino, Santiago Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Schmidt, Gabriela Ines. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Amson, Eli. Universitat Zurich; SuizaFil: Grohé, Camille. American Museum Of Natural History; Estados Unido

The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking

Heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of cancer. Several Hsp90 inhibitors have entered clinical trials. However, some toxicological detriments have arisen, such as cardiotoxicity resulting from hERG inhibition following the administration of Hsp90 inhibitors. We sought to investigate this toxicity as hERG has been previously reported as a client protein that depends upon Hsp90 for its maturation and functional trafficking. In this study we show that hERG depends upon a single Hsp90 isoform. hERG preferentially co-immunoprecipitated with Hsp90α and genetic knockdown of Hsp90α, but not Hsp90β, resulted in a trafficking-defective hERG channel. This study demonstrates the importance of delineating the isoform dependence of Hsp90 client proteins and provides rationale for the design of isoform-selective Hsp90 inhibitors that avoid detrimental effect

Evolutionary Patterns in the Dentition of Duplicidentata (Mammalia) and a Novel Trend in the Molarization of Premolars

The cusp homology of Lagomorpha has long been problematic largely because their teeth are highly derived relative to their more typically tribosphenic ancestors. Within this context, the lagomorph central cusp has been particularly difficult to homologize with other tribosphenic cusps; authors have previously considered it the paracone, protocone, metacone, amphicone, or an entirely new cusp.Here we present newly described fossil duplicidentates (Lagomorpha and Mimotonidae) in the context of a well-constrained phylogeny to establish a nomenclatural system for cusps based on the tribosphenic pattern. We show that the central cusp of lagomorphs is homologous with the metaconule of other mammals. We also show that the buccal acquisition of a second cusp on the premolars (molarization) within duplicidentates is atypical with respect to other mammalian lineages; within the earliest lagomorphs, a second buccal cusp is added mesially to an isolated buccal cusp.The distal shift of the ‘ancestral’ paracone within early duplicidentates amounts to the changing of a paracone into a metacone in these lineages. For this reason, we support a strictly topological approach to cusp names, and suggest a discontinuity in nomenclature to capture the complexity of the interplay between evolutionary history and the developmental process that have produced cusp patterns in duplicidentates

Coverage, Continuity and Visual Cortical Architecture

The primary visual cortex of many mammals contains a continuous representation of visual space, with a roughly repetitive aperiodic map of orientation preferences superimposed. It was recently found that orientation preference maps (OPMs) obey statistical laws which are apparently invariant among species widely separated in eutherian evolution. Here, we examine whether one of the most prominent models for the optimization of cortical maps, the elastic net (EN) model, can reproduce this common design. The EN model generates representations which optimally trade of stimulus space coverage and map continuity. While this model has been used in numerous studies, no analytical results about the precise layout of the predicted OPMs have been obtained so far. We present a mathematical approach to analytically calculate the cortical representations predicted by the EN model for the joint mapping of stimulus position and orientation. We find that in all previously studied regimes, predicted OPM layouts are perfectly periodic. An unbiased search through the EN parameter space identifies a novel regime of aperiodic OPMs with pinwheel densities lower than found in experiments. In an extreme limit, aperiodic OPMs quantitatively resembling experimental observations emerge. Stabilization of these layouts results from strong nonlocal interactions rather than from a coverage-continuity-compromise. Our results demonstrate that optimization models for stimulus representations dominated by nonlocal suppressive interactions are in principle capable of correctly predicting the common OPM design. They question that visual cortical feature representations can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure

Digital reconstruction of the inner ear of Leptictidium auderiense (Leptictida, Mammalia) and North American leptictids reveals new insight into leptictidan locomotor agility

Leptictida are basal Paleocene to Oligocene eutherians from Europe and North America comprising species with highly specialized postcranial features including elongated hind limbs. Among them, the European Leptictidium was probably a bipedal runner or jumper. Because the semicircular canals of the inner ear are involved in detecting angular acceleration of the head, their morphometry can be used as a proxy to elucidate the agility in fossil mammals. Here we provide the first insight into inner ear anatomy and morphometry of Leptictida based on high-resolution computed tomography of a new specimen of Leptictidium auderiense from the middle Eocene Messel Pit (Germany) and specimens of the North American Leptictis and Palaeictops. The general morphology of the bony labyrinth reveals several plesiomorphic mammalian features, such as a secondary crus commune. Leptictidium is derived from the leptictidan groundplan in lacking the secondary bony lamina and having proportionally larger semicircular canals than the leptictids under study. Our estimations reveal that Leptictidium was a very agile animal with agility score values (4.6 and 5.5, respectively) comparable to Macroscelidea and extant bipedal saltatory placentals. Leptictis and Palaeictops have lower agility scores (3.4 to 4.1), which correspond to the more generalized types of locomotion (e.g., terrestrial, cursorial) of most extant mammals. In contrast, the angular velocity magnitude predicted from semicircular canal angles supports a conflicting pattern of agility among leptictidans, but the significance of these differences might be challenged when more is known about intraspecific variation and the pattern of semicircular canal angles in non-primate mammals

The Function Biomedical Informatics Research Network Data Repository

The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical datasets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 dataset consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 Tesla scanners. The FBIRN Phase 2 and Phase 3 datasets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN’s multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data

K+ Channel Regulator KCR1 Suppresses Heart Rhythm by Modulating the Pacemaker Current If

Hyperpolarization-activated, cyclic nucleotide sensitive (HCN) channels underlie the pacemaker current If, which plays an essential role in spontaneous cardiac activity. HCN channel subunits (HCN1-4) are believed to be modulated by additional regulatory proteins, which still have to be identified. Using biochemistry, molecularbiology and electrophysiology methods we demonstrate a protein-protein interaction between HCN2 and the K+ channel regulator protein 1, named KCR1. In coimmunoprecipitation experiments we show that KCR1 and HCN2 proteins are able to associate. Heterologously expressed HCN2 whole-cell current density was significantly decreased by KCR1. KCR1 profoundly suppressed IHCN2 single-channel activity, indicating a functional interaction between KCR1 and the HCN2 channel subunit. Endogenous KCR1 expression could be detected in adult and neonatal rat ventriculocytes. Adenoviral-mediated overexpression of KCR1 in rat cardiomyocytes (i) reduced If whole-cell currents, (ii) suppressed most single-channel gating parameters, (iii) altered the activation kinetics, (iv) suppressed spontaneous action potential activity, and (v) the beating rate. More importantly, siRNA-based knock-down of endogenous KCR1 increased the native If current size and single-channel activity and accelerated spontaneous beating rate, supporting an inhibitory action of endogenous KCR1 on native If. Our observations demonstrate for the first time that KCR1 modulates IHCN2/If channel gating and indicate that KCR1 serves as a regulator of cardiac automaticity