bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to Measure Social Progress?
Authors: Greve Bent 
Published: March 2016

AbstractA good society is the goal for social policy. Recent years have seen a growing awareness that gross domestic product (GDP) alone does not measure this. Happiness and well‐being have increasingly been seen as elements that should influence welfare policies. This review article provides an overview of many of the ways to measure well‐being and happiness. It attempts to cover three distinct, but interrelated subjects. First, why and what can be used to complement GDP as measures for societal development. Second, is there a relation between well‐being, happiness and central social policy areas? Third, whether knowledge on what makes people happy could inform policymakers in their decisions. The article discusses the many new attempts to measure societal development, and the fact that there are so many that decision makers and citizens are drowning by numbers and thereby not able to grasp whether or not there is social progress. Lastly, by using the classical depiction of welfare states, the article analyses whether the indexes are in line herewith, and that, therefore, they might be used as an instrument for steering societies in the direction of a good society.
Vocal Development as a Guide to Modeling the Evolution of Language
Authors: Oller D. Kimbrough , Griebel Ulrike , Warlaumont Anne S. 
Published: March 2016

AbstractModeling of evolution and development of language has principally utilized mature units of spoken language, phonemes and words, as both targets and inputs. This approach cannot address the earliest phases of development because young infants are unable to produce such language features. We argue that units of early vocal development—protophones and their primitive illocutionary/perlocutionary forces—should be targeted in evolutionary modeling because they suggest likely units of hominin vocalization/communication shortly after the split from the chimpanzee/bonobo lineage, and because early development of spontaneous vocal capability is a logically necessary step toward vocal language, a root capability without which other crucial steps toward vocal language capability are impossible. Modeling of language evolution/development must account for dynamic change in early communicative units of form/function across time. We argue for interactive contributions of sender/infants and receiver/caregivers in a feedback loop involving both development and evolution and propose to begin computational modeling at the hominin break from the primate communicative background.
Gene expression profiling of reproductive meristem types in early rice inflorescences by laser microdissection
Authors: Harrop Thomas W. R. , Ud Din Israr , Gregis Veronica , Osnato Michela , Jouannic Stefan , Adam Hélène , Kater Martin M. 
Published: March 2016

SummaryIn rice, inflorescence architecture is established at early stages of reproductive development and contributes directly to grain yield potential. After induction of flowering, the complexity of branching, and therefore the number of seeds on the panicle, is determined by the activity of different meristem types and the timing of transitions between them. Although some of the genes involved in these transitions have been identified, an understanding of the network of transcriptional regulators controlling this process is lacking. To address this we used a precise laser microdissection and RNA‐sequencing approach in Oryza sativa ssp. japonica cv. Nipponbare to produce quantitative data that describe the landscape of gene expression in four different meristem types: the rachis meristem, the primary branch meristem, the elongating primary branch meristem (including axillary meristems), and the spikelet meristem. A switch in expression profile between apical and axillary meristem types followed by more gradual changes during transitions in axillary meristem identity was observed, and several genes potentially involved in branching were identified. This resource will be vital for a mechanistic understanding of the link between inflorescence development and grain yield.
Spike‐dip transformation of Setaria viridis
Authors: Saha Prasenjit , Blumwald Eduardo 
Published: March 2016

SummaryTraditional method of Agrobacterium‐mediated transformation through the generation of tissue culture had limited success for Setaria viridis, an emerging C4 monocot model. Here we present an efficient in planta method for Agrobacterium‐mediated genetic transformation of S. viridis using spike dip. Pre‐anthesis developing spikes were dipped into a solution of Agrobacterium tumefaciens strain AGL1 harboring the β‐glucuronidase (GUS) reporter gene driven by the cauliflower mosaic virus 35S (CaMV35S) promoter to standardize and optimize conditions for transient as well as stable transformations. A transformation efficiency of 0.8 ± 0.1% was obtained after dipping of 5‐day‐old S3 spikes for 20 min in Agrobacterium cultures containing S. viridis spike‐dip medium supplemented with 0.025% Silwet L‐77 and 200 μm acetosyringone. Reproducibility of this method was demonstrated by generating stable transgenic lines expressing β‐glucuronidase plus (GUSplus), green fluorescent protein (GFP) and Discosoma sp. red fluorescent protein (DsRed) reporter genes driven by either CaMV35S or intron‐interrupted maize ubiquitin (Ubi) promoters from three S. viridis genotypes. Expression of these reporter genes in transient assays as well as in T1 stable transformed plants was monitored using histochemical, fluorometric GUS activity and fluorescence microscopy. Molecular analysis of transgenic lines revealed stable integration of transgenes into the genome, and inherited transgenes expressed in the subsequent generations. This approach provides opportunities for the high‐throughput transformation and potentially facilitates translational research in a monocot model plant.
Cooperation between the chloroplast psbA 5′‐untranslated region and coding region is important for translational initiation: the chloroplast translation machinery cannot read a human viral gene coding region
Authors: Nakamura Masayuki , Hibi Yurina , Okamoto Takashi , Sugiura Masahiro 
Published: March 2016

SummaryChloroplast mRNA translation is regulated by the 5′‐untranslated region (5′‐UTR). Chloroplast 5′‐UTRs also support translation of the coding regions of heterologous genes. Using an in vitro translation system from tobacco chloroplasts, we detected no translation from a human immunodeficiency virus tat coding region fused directly to the tobacco chloroplast psbA 5′‐UTR. This lack of apparent translation could have been due to rapid degradation of mRNA templates or synthesized protein products. Replacing the psbA 5′‐UTR with the E. coli phage T7 gene 10 5′‐UTR, a highly active 5′‐UTR, and substituting synonymous codons led to some translation of the tat coding region. The Tat protein thus synthesized was stable during translation reactions. No significant degradation of the added tat mRNAs was observed after translation reactions. These results excluded the above two possibilities and confirmed that the tat coding region prevented its own translation. The tat coding region was then fused to the psbA 5′‐UTR with a cognate 5′‐coding segment. Significant translation was detected from the tat coding region when fused after 10 or more codons. That is, translation could be initiated from the tat coding region once translation had started, indicating that the tat coding region inhibits translational initiation but not elongation. Hence, cooperation/compatibility between the 5′‐UTR and its coding region is important for translational initiation.
Exercise training improves obesity‐related lymphatic dysfunction
Authors: Hespe Geoffrey E. , Kataru Raghu P. , Savetsky Ira L. , García Nores Gabriela D. , Torrisi Jeremy S. , Nitti Matthew D. , Gardenier Jason C. , Zhou Jie , Yu Jessie Z. , Jones Lee W. , Mehrara Babak J. 
Published: March 2016

Key pointsObesity results in perilymphatic inflammation and lymphatic dysfunction.Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells.Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells.AbstractAlthough previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (allP < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti‐inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, includingVEGFR‐3andProx1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity‐induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications.
Revolutionary Science
Authors: Casadevall Arturo , Fang Ferric C. 
Published: March 2016

ABSTRACT
On rare occasions in the history of science, remarkable discoveries transform human society and forever alter mankind’s view of the world. Examples of such discoveries include the heliocentric theory, Newtonian physics, the germ theory of disease, quantum theory, plate tectonics and the discovery that DNA carries genetic information. The science philosopher Thomas Kuhn famously described science as long periods of normality punctuated by times of crisis, when anomalous observations culminate in revolutionary changes that replace one paradigm with another. This essay examines several transformative discoveries in the light of Kuhn’s formulation. We find that each scientific revolution is unique, with disparate origins that may include puzzle solving, serendipity, inspiration, or a convergence of disparate observations. The causes of revolutionary science are varied and lack an obvious common structure. Moreover, it can be difficult to draw a clear distinction between so-called normal and revolutionary science. Revolutionary discoveries often emerge from basic science and are critically dependent on nonrevolutionary research. Revolutionary discoveries may be conceptual or technological in nature, lead to the creation of new fields, and have a lasting impact on many fields in addition to the field from which they emerge. In contrast to political revolutions, scientific revolutions do not necessarily require the destruction of the previous order. For humanity to continue to benefit from revolutionary discoveries, a broad palette of scientific inquiry with a particular emphasis on basic science should be supported.
Complex Interplay of the
UL136
Isoforms Balances Cytomegalovirus Replication and Latency
Authors: Caviness Katie , Bughio Farah , Crawford Lindsey B. , Streblow Daniel N. , Nelson Jay A. , Caposio Patrizia , Goodrum Felicia 
Published: March 2016

ABSTRACT

Human cytomegalovirus (HCMV), a betaherpesvirus, persists indefinitely in the human host through poorly understood mechanisms. The
UL136
gene is carried within a genetic locus important to HCMV latency termed the
UL133
/
8
locus, which also carries
UL133
,
UL135
, and
UL138
. Previously, we demonstrated that
UL136
is expressed as five protein isoforms ranging from 33-kDa to 19-kDa, arising from alternative transcription and, likely, translation initiation mechanisms. We previously showed that the
UL136
isoforms are largely dispensable for virus infection in fibroblasts, a model for productive virus replication. In our current work,
UL136
has emerged as a complex regulator of HCMV infection in multiple contexts of infection relevant to HCMV persistence: in an endothelial cell (EC) model of chronic infection, in a CD34
+
hematopoietic progenitor cell (HPC) model of latency, and in an
in vivo
NOD-
scid
IL2Rγ
c
null
humanized (huNSG) mouse model for latency. The 33- and 26-kDa isoforms promote replication, while the 23- and 19-kDa isoforms suppress replication in ECs, in CD34
+
HPCs, and in huNSG mice. The role of the 25-kDa isoform is context dependent and influences the activity of the other isoforms. These isoforms localize throughout the secretory pathway, and loss of the 33- and 26-kDa
UL136
isoforms results in virus maturation defects in ECs. This work reveals an intriguing functional interplay between protein isoforms that impacts virus replication, latency, and dissemination, contributing to the overall role of the
UL133
/
8
locus in HCMV infection.

IMPORTANCE
The persistence of DNA viruses, and particularly of herpesviruses, remains an enigma because we have not completely defined the viral and host factors important to persistence. Human cytomegalovirus, a herpesvirus, persists in the absence of disease in immunocompetent individuals but poses a serious disease threat to transplant patients and the developing fetus. There is no vaccine, and current therapies do not target latent reservoirs. In an effort to define the viral factors important to persistence, we have studied viral genes with no known viral replication function in contexts important to HCMV persistence. Using models relevant to viral persistence, we demonstrate opposing roles of protein isoforms encoded by the
UL136
gene in regulating latent and replicative states of infection. Our findings reveal an intriguing interplay between
UL136
protein isoforms and define
UL136
as an important regulator of HCMV persistence.
Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in
Bordetella
Authors: Lesne E. , Krammer E.-M. , Dupre E. , Locht C. , Lensink M. F. , Antoine R. , Jacob-Dubuisson F. 
Published: March 2016

ABSTRACT

The two-component system BvgAS controls the expression of the virulence regulon of
Bordetella pertussis
. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS) domain and then a predicted 2-helix coiled coil that precede the dimerization-histidine-phosphotransfer domain of the kinase. BvgS homologs have a similar domain organization, or they harbor only a predicted coiled coil between the transmembrane and the dimerization-histidine-phosphotransfer domains. Here, we show that the 2-helix coiled coil of BvgS regulates the enzymatic activity in a mechanical manner. Its marginally stable hydrophobic interface enables a switch between a state of great rotational dynamics in the kinase mode and a more rigid conformation in the phosphatase mode in response to signal perception by the periplasmic domains. We further show that the activity of BvgS is controlled in the same manner if its PAS domain is replaced with the natural α-helical sequences of PAS-less homologs. Clamshell motions of the Venus flytrap domains trigger the shift of the coiled coil’s dynamics. Thus, we have uncovered a general mechanism of regulation for the BvgS family of Venus flytrap-containing two-component sensor kinases.

IMPORTANCE
The two-component system BvgAS of the whooping cough agent
Bordetella pertussis
regulates the virulence factors necessary for infection in a coordinated manner. BvgS is the prototype of a family of sensor kinase proteins found in major bacterial pathogens. When BvgS functions as a kinase,
B. pertussis
is virulent, and the bacterium shifts to an avirulent phase after BvgS senses chemicals that make it switch to phosphatase. Our goal is to decipher the signaling mechanisms of BvgS in order to understand virulence regulation in
Bordetella
, which may lead to new antimicrobial treatments targeting those two-component systems. We discovered that the activity of BvgS is regulated in a mechanical manner. A short region of the protein that precedes the enzymatic domain switches between two states in response to signal perception by other BvgS domains. This switch region is conserved among BvgS homologs, and thus, the regulation uncovered here will likely be relevant for the family.
Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System
Authors: Bhuwan Manish , Arora Naresh , Sharma Ashish , Khubaib Mohd , Pandey Saurabh , Chaudhuri Tapan Kumar , Hasnain Seyed Ehtesham , Ehtesham Nasreen Zafar 
Published: March 2016

ABSTRACT

Mycobacterium tuberculosis
is a leading cause of death worldwide. The
M. tuberculosis
TAT (twin-arginine translocation) protein secretion system is present at the cytoplasmic membrane of mycobacteria and is known to transport folded proteins. The TAT secretion system is reported to be essential for many important bacterial processes that include cell wall biosynthesis. The
M. tuberculosis
secretion and invasion protein RipA has endopeptidase activity and interacts with one of the resuscitation antigens (RpfB) that are expressed during pathogen reactivation. MoxR1, a member of the ATPase family that is associated with various cellular activities, was predicted to interact with RipA based on
in silico
analyses. A bimolecular fluorescence complementation (BiFC) assay confirmed the interaction of these two proteins in HEK293T cells. The overexpression of RipA in
Mycobacterium smegmatis
and copurification with MoxR1 further validated their interaction
in vivo
. Recombinant MoxR1 protein, expressed in
Escherichia coli
, displays ATP-enhanced chaperone activity. Secretion of recombinant RipA (rRipA) protein into the
E. coli
culture filtrate was not observed in the absence of RipA-MoxR interaction. Inhibition of this export system in
M. tuberculosis
, including the key players, will prevent localization of peptidoglycan hydrolase and result in sensitivity to existing β-lactam antibiotics, opening up new candidates for drug repurposing.

IMPORTANCE
The virulence mechanism of mycobacteria is very complex. Broadly, the virulence factors can be classified as secretion factors, cell surface components, enzymes involved in cellular metabolism, and transcriptional regulators. The mycobacteria have evolved several mechanisms to secrete its proteins. Here, we have identified one of the virulence proteins of
Mycobacterium tuberculosis
, RipA, possessing peptidoglycan hydrolase activities secreted by the TAT secretion pathway. We also identified MoxR1 as a protein-protein interaction partner of RipA and demonstrated chaperone activity of this protein. We show that MoxR1-mediated folding is critical for the secretion of RipA within the TAT system. Inhibition of this export system in
M. tuberculosis
will prevent localization of peptidoglycan hydrolase and result in sensitivity to existing β-lactam antibiotics, opening up new candidates for drug repurposing.
Loss of Multicellular Behavior in Epidemic African Nontyphoidal Salmonella enterica Serovar Typhimurium ST313 Strain D23580
Authors: Singletary Larissa A. , Karlinsey Joyce E. , Libby Stephen J. , Mooney Jason P. , Lokken Kristen L. , Tsolis Renée M. , Byndloss Mariana X. , Hirao Lauren A. , Gaulke Christopher A. , Crawford Robert W. , Dandekar Satya , Kingsley Robert A. , Msefula Chisomo L. , Heyderman Robert S. , Fang Ferric C. 
Published: March 2016

ABSTRACT

Nontyphoidal
Salmonella enterica
serovar Typhimurium is a frequent cause of bloodstream infections in children and HIV-infected adults in sub-Saharan Africa. Most isolates from African patients with bacteremia belong to a single sequence type, ST313, which is genetically distinct from gastroenteritis-associated ST19 strains, such as 14028s and SL1344. Some studies suggest that the rapid spread of ST313 across sub-Saharan Africa has been facilitated by anthroponotic (person-to-person) transmission, eliminating the need for
Salmonella
survival outside the host. While these studies have not ruled out zoonotic or other means of transmission, the anthroponotic hypothesis is supported by evidence of extensive genomic decay, a hallmark of host adaptation, in the sequenced ST313 strain D23580. We have identified and demonstrated 2 loss-of-function mutations in D23580, not present in the ST19 strain 14028s, that impair multicellular stress resistance associated with survival outside the host. These mutations result in inactivation of the KatE stationary-phase catalase that protects high-density bacterial communities from oxidative stress and the BcsG cellulose biosynthetic enzyme required for the RDAR (red, dry, and rough) colonial phenotype. However, we found that like 14028s, D23580 is able to elicit an acute inflammatory response and cause enteritis in mice and rhesus macaque monkeys. Collectively, these observations suggest that African
S
. Typhimurium ST313 strain D23580 is becoming adapted to an anthroponotic mode of transmission while retaining the ability to infect and cause enteritis in multiple host species.

IMPORTANCE
The last 3 decades have witnessed an epidemic of invasive nontyphoidal
Salmonella
infections in sub-Saharan Africa. Genomic analysis and clinical observations suggest that the
Salmonella
strains responsible for these infections are evolving to become more typhoid-like with regard to patterns of transmission and virulence. This study shows that a prototypical African nontyphoidal
Salmonella
strain has lost traits required for environmental stress resistance, consistent with an adaptation to a human-to-human mode of transmission. However, in contrast to predictions, the strain remains capable of causing acute inflammation in the mammalian intestine. This suggests that the systemic clinical presentation of invasive nontyphoidal
Salmonella
infections in Africa reflects the immune status of infected hosts rather than intrinsic differences in the virulence of African
Salmonella
strains. Our study provides important new insights into the evolution of host adaptation in bacterial pathogens.