The Wiring Economy Principle: Connectivity Determines Anatomy in the Human Brain

Minimization of the wiring cost of white matter fibers in the human brain appears to be an organizational principle. We investigate this aspect in the human brain using whole brain connectivity networks extracted from high resolution diffusion MRI data of 14 normal volunteers. We specifically address the question of whether brain anatomy determines its connectivity or vice versa. Unlike previous studies we use weighted networks, where connections between cortical nodes are real-valued rather than binary off-on connections. In one set of analyses we found that the connectivity structure of the brain has near optimal wiring cost compared to random networks with the same number of edges, degree distribution and edge weight distribution. A specifically designed minimization routine could not find cheaper wiring without significantly degrading network performance. In another set of analyses we kept the observed brain network topology and connectivity but allowed nodes to freely move on a 3D manifold topologically identical to the brain. An efficient minimization routine was written to find the lowest wiring cost configuration. We found that beginning from any random configuration, the nodes invariably arrange themselves in a configuration with a striking resemblance to the brain. This confirms the widely held but poorly tested claim that wiring economy is a driving principle of the brain. Intriguingly, our results also suggest that the brain mainly optimizes for the most desirable network connectivity, and the observed brain anatomy is merely a result of this optimization

Plus- and Minus-End Directed Microtubule Motors Bind Simultaneously to Herpes Simplex Virus Capsids Using Different Inner Tegument Structures

Many viruses depend on host microtubule motors to reach their destined intracellular location. Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 (HSV1) show bidirectional transport towards the cell center as well as the periphery, indicating that they utilize microtubule motors of opposing directionality. To understand the mechanisms of specific motor recruitment, it is necessary to characterize the molecular composition of such motile viral structures. We have generated HSV1 capsids with different surface features without impairing their overall architecture, and show that in a mammalian cell-free system the microtubule motors dynein and kinesin-1 and the dynein cofactor dynactin could interact directly with capsids independent of other host factors. The capsid composition and surface was analyzed with respect to 23 structural proteins that are potentially exposed to the cytosol during virus assembly or cell entry. Many of these proteins belong to the tegument, the hallmark of all herpesviruses located between the capsid and the viral envelope. Using immunoblots, quantitative mass spectrometry and quantitative immunoelectron microscopy, we show that capsids exposing inner tegument proteins such as pUS3, pUL36, pUL37, ICP0, pUL14, pUL16, and pUL21 recruited dynein, dynactin, kinesin-1 and kinesin-2. In contrast, neither untegumented capsids exposing VP5, VP26, pUL17 and pUL25 nor capsids covered by outer tegument proteins such as vhs, pUL11, ICP4, ICP34.5, VP11/12, VP13/14, VP16, VP22 or pUS11 bound microtubule motors. Our data suggest that HSV1 uses different structural features of the inner tegument to recruit dynein or kinesin-1. Individual capsids simultaneously accommodated motors of opposing directionality as well as several copies of the same motor. Thus, these associated motors either engage in a tug-of-war or their activities are coordinately regulated to achieve net transport either to the nucleus during cell entry or to cytoplasmic membranes for envelopment during assembly

First beta-decay spectroscopy of In-135 and new beta-decay branches of In-134

The beta decay of the neutron-rich In-134 and In-135 was investigated experimentally in order to provide new insights into the nuclear structure of the tin isotopes with magic proton number Z = 50 above the N = 82 shell. The beta-delayed gamma-ray spectroscopy measurement was performed at the ISOLDE facility at CERN, where indium isotopes were selectively laser-ionized and on-line mass separated. Three beta-decay branches of In-134 were established, two of which were observed for the first time. Population of neutron-unbound states decaying via. rays was identified in the two daughter nuclei of In-134, Sn-134 and Sn-133, at excitation energies exceeding the neutron separation energy by 1 MeV. The beta-delayed one- and two-neutron emission branching ratios of In-134 were determined and compared with theoretical calculations. The beta-delayed one-neutron decay was observed to be dominant beta-decay branch of In-134 even though the Gamow-Teller resonance is located substantially above the two-neutron separation energy of Sn-134. Transitions following the beta decay of In-135 are reported for the first time, including. rays tentatively attributed to Sn-135. In total, six new levels were identified in Sn-134 on the basis of the beta.. coincidences observed in the In-134 and In-135 beta decays. A transition that might be a candidate for deexciting the missing neutron single-particle 13/2(+) state in Sn-133 was observed in both beta decays and its assignment is discussed. Experimental level schemes of Sn-134 and Sn-135 are compared with shell-model predictions. Using the fast timing technique, half-lives of the 2(+), 4(+), and 6(+) levels in Sn-134 were determined. From the lifetime of the 4(+) state measured for the first time, an unexpectedly large B(E2; 4(+)-> 2(+)) transition strength was deduced, which is not reproduced by the shell-model calculations.Peer reviewe

Externalizing, internalizing and fostering commitment: the case of born-global firms in emerging economies

This paper examines the HR practices of mature born-global firms from twenty-nine emerging economies. Through an examination of large scale survey data the paper questions the extent to which firm size impacts the employment of temporary workers, the employment of skilled workers and the extent of employee training. Findings suggest that as firm size increases the use of temporary workers decreases, the number of skilled workers increases and the number of employees receiving training also increases. The paper highlights how born-global firms are able to shift away from externalized, market-based approaches towards more internalized, commitment-based approaches in order to survive, adapt and grow

Protective management of trees against debarking by deer negatively impacts bryophyte diversity

When wildlife populations become too large, they impact other flora and fauna within the ecosystems that they inhabit. For example, the recent rise in population numbers of sika deer in Japan has led to the stripping of bark from tree overstories in forested areas. This has led to protective management actions, such as wrapping the trunks of trees in wire mesh. The present study investigates the impact of this management action on epiphytic diversity at Mt. Ohdaigahara, which is one of the hotspots for bryophyte diversity in Japan. The correlation between the diversity of epiphytic bryophytes and environmental variables was examined, including the presence/absence of wire mesh protection. A generalized linear model showed that species richness and bryophyte cover was significantly correlated with both tree diameter (at 1.5 m height) and tree density (P < 0.01), but negatively correlated with wire mesh protection. Inductively coupled plasma-mass spectrometry analysis showed a significant 3- to 6-fold higher concentration of zinc in bryophytes occupying tree bark under wire mesh protection than for those without wire mesh. Hence, the high sensitivity of bryophytes to zinc accumulation, as a result of toxicity caused by galvanized iron mesh, has led to the loss of species richness and bryophyte cover on tree trunks. Furthermore, other heavy metals found in wire mesh may also contribute to the negative effect on bryophytes. Therefore, to establish best practices for biodiversity conservation that include bryophytes, materials that are free of heavy metals should be preferentially used for tree protection

Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python.(TABLE)Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013').This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product.This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike

AAV ancestral reconstruction library enables selection of broadly infectious viral variants

Adeno-associated virus (AAV) vectors have achieved clinical efficacy in treating several diseases. However, enhanced vectors are required to extend these landmark successes to other indications and protein engineering approaches may provide the necessary vector improvements to address such unmet medical needs. To generate new capsid variants with potentially enhanced infectious properties and to gain insights into AAV's evolutionary history, we computationally designed and experimentally constructed a putative ancestral AAV library. Combinatorial variations at 32 amino acid sites were introduced to account for uncertainty in their identities. We then analyzed the evolutionary flexibility of these residues, the majority of which have not been previously studied, by subjecting the library to iterative selection on a representative cell line panel. The resulting variants exhibited transduction efficiencies comparable to the most efficient extant serotypes and, in general, ancestral libraries were broadly infectious across the cell line panel, indicating that they favored promiscuity over specificity. Interestingly, putative ancestral AAVs were more thermostable than modern serotypes and did not use sialic acids, galactose or heparan sulfate proteoglycans for cellular entry. Finally, variants mediated 19- to 31-fold higher gene expression in the muscle compared with AAV1, a clinically used serotype for muscle delivery, highlighting their promise for gene therapy

AAV ancestral reconstruction library enables selection of broadly infectious viral variants

Adeno-associated virus (AAV) vectors have achieved clinical efficacy in treating several diseases. However, enhanced vectors are required to extend these landmark successes to other indications and protein engineering approaches may provide the necessary vector improvements to address such unmet medical needs. To generate new capsid variants with potentially enhanced infectious properties and to gain insights into AAV's evolutionary history, we computationally designed and experimentally constructed a putative ancestral AAV library. Combinatorial variations at 32 amino acid sites were introduced to account for uncertainty in their identities. We then analyzed the evolutionary flexibility of these residues, the majority of which have not been previously studied, by subjecting the library to iterative selection on a representative cell line panel. The resulting variants exhibited transduction efficiencies comparable to the most efficient extant serotypes and, in general, ancestral libraries were broadly infectious across the cell line panel, indicating that they favored promiscuity over specificity. Interestingly, putative ancestral AAVs were more thermostable than modern serotypes and did not use sialic acids, galactose or heparan sulfate proteoglycans for cellular entry. Finally, variants mediated 19- to 31-fold higher gene expression in the muscle compared with AAV1, a clinically used serotype for muscle delivery, highlighting their promise for gene therapy

Opportunity exploitation in software startups:a human capital view

Abstract Background: Transforming a business opportunity to a valid business case is a crucial process of an early-stage software startups. Prior literature on entrepreneurship defines two types of opportunity exploitations, opportunity discovery and opportunity creation, and proposes models describing the exploitation processes. The factors affecting startups’ abilities to conduct the exploitation are, however, addressed only to a limited extend in prior research. Aim: This research aims at increasing the knowledge on those factors by studying empirically the effects of the available human capital on the opportunity exploitation processes in software startups. Method: We conducted a multiple-case study on a group of software startups in Italy, Norway and Finland. We focused on the founders of the startups, examining their opportunity processes, their human capital, and the interdependencies between the opportunity processes and human capital. Results: Our results are in line with the findings of prior research, which point out that uncertainty is the key differentiator between the opportunity discovery and creation processes. The results reveal, however, that both process types co-exist in the early stages of software startups, independently of how the opportunity was initially recognized, and also highlight missing human capital as a key reason for the uncertainty. We conclude that in software startups the availability of human capital plays a bigger role in the exploitation of opportunities than their types, discovered or created, because even exploitation of a-priori existing opportunities turn to opportunity creation processes in case of human capital hortages