bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth, feed intake and carcass characteristics of indigenous goats fed local resources in Tunisian arid land
Authors: Ayeb N. , Seddik M. , Atti N. , Atigui M. , Fguiri I. , Barmat A. , Arroum S. , Addis M. , Hammadi M. , Khorchani T.
Published: July 2015

Native genetic resource of goats is a pivotal source for meat and milk in southern Tunisia. Feeding is one of the most important activities of goat husbandry. Perceptions on the role of native feed resources for growth and carcass characteristics have not been well studied. Therefore, the present study was designed to help understand and to compare the influences of local forage resources (grass hay, dried olive leaves, Stipa tenacissima and oat hay) on growth performance and carcass characteristics of kids. The kids with the age of 4 months (average live bodyweight of 15 ± 58 kg) were selected for the study. The three study groups in the 90-day trial were as follows: Group C, where animals received oat hay only (control), Group OL, where animals received olive leaves (dried) + S. tenacissima and Group GH, where animals received grass hay. A daily allowance of commercially available concentrate (305 g DM/day) was offered to all groups (making about half of the total DM intake). At the end of the experiment, all animals were slaughtered. Statistical analysis showed that total DM intake was lower (P < 0.001) in C group (490.77 g) than the other two groups having similar DM intake (619.22 and 589.28 g for OL and GH, respectively). Average daily gain was comparable for the three groups (38.33, 40.71 g and 39.52, respectively, for C, OL and GH), with similar final liveweights. Cold carcass weight and carcass yield were not affected by diet treatment. Diet had no significant effect on individual organ weights and carcass composition. The use of the local forage resources evaluated in this trial could be used for the local goat population without loss of productivity when they make up about half of the diet along with a concentrate feed.
The Importance of Motions that Accompany Those Occurring Along the Reaction Coordinate
Authors: Reimers Jeffrey R.
Published: July 2015

The reaction coordinate is a well known quantity used to define the motions critical to chemical reactions, but many other motions always accompany it. These other motions are typically ignored but this is not always possible. Sometimes it is not even clear as to which motions comprise the reaction coordinate: spectral measurements that one may assume are dominated by the reaction coordinate could instead be dominated by the accompanying modes. Examples of different scenarios are considered. The assignment of the visible absorption spectrum of chlorophyll-a was debated for 50 years, with profound consequences for the understanding of how light energy is transported and harvested in natural and artificial solar-energy devices. We recently introduced a new, comprehensive, assignment, the centrepiece of which was determination of the reaction coordinate for an unrecognized photochemical process. The notion that spectroscopy and reactivity are so closely connected comes directly from Hush’s adiabatic theory of electron-transfer reactions. Its basic ideas are reviewed, similarities to traditional chemical theories drawn, key analytical results described, and the importance of the accompanying modes stressed. Also highlighted are recent advances that allow this theory to be applied to general transformations including isomerization processes, hybridization, aromaticity, hydrogen bonding, and understanding why the properties of first-row molecules such as NH3 (bond angle 108°) are so different to those of PH3–BiH3 (bond angles 90–93°). Historically, the question of what is the reaction coordinate and what is just an accompanying motion has not commonly been at the forefront of attention. In our new approach in which all chemical processes are described using the same core theory, this question becomes thrust forward as always being the most important qualitative feature to determine.
Force generation by the growth of amyloid aggregates
Authors: Herling Therese W. , Garcia Gonzalo A. , Michaels Thomas C. T. , Grentz Wolfgang , Dean James , Shimanovich Ulyana , Gang Hongze , Müller Thomas , Kav Batuhan , Terentjev Eugene M. , Dobson Christopher M. , Knowles Tuomas P. J.
Published: July 2015

Significance

Force generation by active biological materials, in particular through native protein polymerization, is a key feature of cellular function and motility. Protein polymerization to form amyloid fibrils is associated with a number of devastating and currently incurable protein misfolding diseases. Unlike the polymerization of actin and tubulin driving cell motility, little is known about the mechanical properties of amyloid fibril growth. Here, we present direct experimental measurements of the force generated by growing amyloid fibrils. These measurements demonstrate that amyloid growth can release comparable forces to actin and tubulin polymerization. This conclusion is remarkable as actin and tubulin, unlike proteins forming amyloid fibrils, have evolved to generate force.
Mitochondrial genomes are retained by selective constraints on protein targeting
Authors: Björkholm Patrik , Harish Ajith , Hagström Erik , Ernst Andreas M. , Andersson Siv G. E.
Published: July 2015

Mitochondria are energy-producing organelles in eukaryotic cells considered to be of bacterial origin. The mitochondrial genome has evolved under selection for minimization of gene content, yet it is not known why not all mitochondrial genes have been transferred to the nuclear genome. Here, we predict that hydrophobic membrane proteins encoded by the mitochondrial genomes would be recognized by the signal recognition particle and targeted to the endoplasmic reticulum if they were nuclear-encoded and translated in the cytoplasm. Expression of the mitochondrially encoded proteins Cytochrome oxidase subunit 1, Apocytochrome
b
, and ATP synthase subunit 6 in the cytoplasm of HeLa cells confirms export to the endoplasmic reticulum. To examine the extent to which the mitochondrial proteome is driven by selective constraints within the eukaryotic cell, we investigated the occurrence of mitochondrial protein domains in bacteria and eukaryotes. The accessory protein domains of the oxidative phosphorylation system are unique to mitochondria, indicating the evolution of new protein folds. Most of the identified domains in the accessory proteins of the ribosome are also found in eukaryotic proteins of other functions and locations. Overall, one-third of the protein domains identified in mitochondrial proteins are only rarely found in bacteria. We conclude that the mitochondrial genome has been maintained to ensure the correct localization of highly hydrophobic membrane proteins. Taken together, the results suggest that selective constraints on the eukaryotic cell have played a major role in modulating the evolution of the mitochondrial genome and proteome.
Robust network oscillations during mammalian respiratory rhythm generation driven by synaptic dynamics
Authors: Guerrier Claire , Hayes John A. , Fortin Gilles , Holcman David
Published: July 2015

Significance

The mechanism underlying mammalian respiratory rhythm generation in the preBötzinger complex is still under debate. Here, we developed a simulation model to show that a synaptic depression/facilitation mechanism sufficient for neurons to generate network rhythms, without the need for intrinsically rhythmic neurons. Simulations of the model under several normal or pathological conditions the living system experiences, together with critical electrophysiological experiments, converge to show that randomly connected neuronal networks with synaptic dynamics underlie rhythmic activity. This study provides a generally applicable mechanism for other central pattern generator systems that are less well understood.
Multiethnicity, pluralism, and migration in the south central Andes: An alternate path to state expansion
Authors: Goldstein Paul S.
Published: July 2015

The south central Andes is known as a region of enduring multiethnic diversity, yet it is also the cradle of one the South America’s first successful expansive-state societies. Social structures that encouraged the maintenance of separate identities among coexistent ethnic groups may explain this apparent contradiction. Although the early expansion of the Tiwanaku state (A.D. 600–1000) is often interpreted according to a centralized model derived from Old World precedents, recent archaeological research suggests a reappraisal of the socio-political organization of Tiwanaku civilization, both for the diversity of social entities within its core region and for the multiple agencies behind its wider program of agropastoral colonization. Tiwanaku’s sociopolitical pluralism in both its homeland and colonies tempers some of archaeology’s global assumptions about the predominant role of centralized institutions in archaic states.
Clonality and intracellular polyploidy in virus evolution and pathogenesis
Authors: Perales Celia , Moreno Elena , Domingo Esteban
Published: July 2015

In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.
Artificial cloning of domestic animals
Authors: Keefer Carol L.
Published: July 2015

Domestic animals can be cloned using techniques such as embryo splitting and nuclear transfer to produce genetically identical individuals. Although embryo splitting is limited to the production of only a few identical individuals, nuclear transfer of donor nuclei into recipient oocytes, whose own nuclear DNA has been removed, can result in large numbers of identical individuals. Moreover, clones can be produced using donor cells from sterile animals, such as steers and geldings, and, unlike their genetic source, these clones are fertile. In reality, due to low efficiencies and the high costs of cloning domestic species, only a limited number of identical individuals are generally produced, and these clones are primarily used as breed stock. In addition to providing a means of rescuing and propagating valuable genetics, somatic cell nuclear transfer (SCNT) research has contributed knowledge that has led to the direct reprogramming of cells (e.g., to induce pluripotent stem cells) and a better understanding of epigenetic regulation during embryonic development. In this review, I provide a broad overview of the historical development of cloning in domestic animals, of its application to the propagation of livestock and transgenic animal production, and of its scientific promise for advancing basic research.
Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt
+
NIK
+
signalosome on Rab5
+
endosomes
Authors: Jane-wit Dan , Surovtseva Yulia V. , Qin Lingfeng , Li Guangxin , Liu Rebecca , Clark Pamela , Manes Thomas D. , Wang Chen , Kashgarian Michael , Kirkiles-Smith Nancy C. , Tellides George , Pober Jordan S.
Published: July 2015

Significance

Complement activation contributes to host defense and immunopathology. We recently discovered that membrane attack complexes (MAC), the terminal effector mechanisms of complement, activate proinflammatory functions in human endothelial cells (ECs) via noncanonical NF-ΚB signaling. Here we elucidate the initial steps of how MACs activate this pathway. MACs formed on the surface of human ECs are rapidly internalized via clathrin-mediated endocytosis into Rab5
+
endosomes, which subsequently recruit activated Akt in a Rab5-dependent manner. Akt recruitment results in NIK protein stabilization on the surface of the endosome within 30 min, initiating noncanonical NF-ΚB signaling. MAC internalization in ECs lining human coronary arteries in vivo similarly activates noncanonical NF-ΚB signaling. Our findings suggest new therapeutic targets for controlling complement-mediated inflammation.
Toward a theory of punctuated subsistence change
Authors: Ullah Isaac I. T. , Kuijt Ian , Freeman Jacob
Published: July 2015

Significance

The questions of how, when, and why humans transitioned from hunting and gathering to food production are important to understand the evolution and sustainability of agricultural economies. We explore cross-cultural data on human subsistence with multivariate techniques and interpret the results from the perspective of human societies as complex adaptive systems. We gain insight into several controlling variables that may inordinately influence the possibilities for subsistence change and into why the forager–farmer transition occurred quickly in some cases and more gradually in others.
Stress controls the mechanics of collagen networks
Authors: Licup Albert James , Münster Stefan , Sharma Abhinav , Sheinman Michael , Jawerth Louise M. , Fabry Ben , Weitz David A. , MacKintosh Fred C.
Published: July 2015

Significance

We report nonlinear rheology experiments on collagen type I networks, which demonstrate a surprising concentration independence of the network stiffness in the nonlinear elastic regime. We develop a model that can account for this, as well as the classical observations of an approximate exponential stress–strain relationship in collagenous tissues, for which a microscopic model has been lacking. Our model also demonstrates the importance of normal stresses in controlling the nonlinear mechanics of fiber networks.
Plasmid replication initiator interactions with origin 13-mers and polymerase subunits contribute to strand-specific replisome assembly
Authors: Wawrzycka Aleksandra , Gross Marta , Wasaznik Anna , Konieczny Igor
Published: July 2015

Significance

Research on DNA replication initiation has not revealed the exact mechanism for replication complex de novo assembly at the origin or how the directionality of replication is determined. To date, no evidence for direct involvement of a replication initiation protein (Rep) in the process of polymerase recruitment has been reported. This work demonstrates that a plasmid Rep, in addition to its already described functions in origin opening and helicase recruitment, can serve as a DNA polymerase anchoring factor. Through its interaction with 13-mer sequences on one strand of initially unwound DNA and interactions with the subunits of DNA polymerase, the initiation protein facilitates strand-specific replisome assembly at the replication origin. This step determines the direction of DNA replication.
Burst pacemaker activity of the sinoatrial node in sodium–calcium exchanger knockout mice
Authors: Torrente Angelo G. , Zhang Rui , Zaini Audrey , Giani Jorge F. , Kang Jeanney , Lamp Scott T. , Philipson Kenneth D. , Goldhaber Joshua I.
Published: July 2015

Significance

The sinoatrial node (SAN) generates cardiac pacemaker activity through the interplay of membrane ionic currents and intracellular calcium cycling. SAN dysfunction is a common disorder that usually requires implantation of costly electronic pacemakers. To study the role of intracellular calcium regulation by the sodium/calcium exchanger (NCX) in SAN pacing, we generated an atrial-specific NCX knockout mouse. The SAN beating pattern in these mice is abnormal, with bursts of activity interrupted by frequent pauses reminiscent of clinical SAN disease. We found that cellular calcium accumulation was responsible for this abnormal beating pattern, underscoring the importance of NCX-mediated calcium efflux to normal pacing. We propose that burst firing is a common feature of SAN dysfunction caused by elevated cytoplasmic calcium.
Entner–Doudoroff pathway for sulfoquinovose degradation in
Pseudomonas putida
SQ1
Authors: Felux Ann-Katrin , Spiteller Dieter , Klebensberger Janosch , Schleheck David
Published: July 2015

Significance

Phototrophic organisms worldwide produce estimated 10 gigatons of sulfoquinovose (SQ) per year; hence, complete degradation of SQ by bacteria is an important part of the biogeochemical sulfur cycle. Here, we show that
Pseudomonas putida
SQ1 catabolizes SQ to 3-sulfolactate (SL) in analogy to the Entner–Doudoroff pathway for glucose-6-phosphate, involving five newly discovered reactions, enzymes, and genes, and three newly discovered organosulfur intermediates. The SL can be mineralized by other bacteria, thus closing the sulfur cycle within a bacterial community. The genes for the SQ Entner–Doudoroff pathway can be found in genomes of a wide range of Proteobacteria, which shows that SQ utilization is a widespread and important, but still underrecognized, trait of bacteria in all environments where SQ is produced and degraded.
Toward a sustainable biomedical research enterprise: Finding consensus and implementing recommendations
Authors: Pickett Christopher L. , Corb Benjamin W. , Matthews C. Robert , Sundquist Wesley I. , Berg Jeremy M.
Published: July 2015

The US research enterprise is under significant strain due to stagnant funding, an expanding workforce, and complex regulations that increase costs and slow the pace of research. In response, a number of groups have analyzed the problems and offered recommendations for resolving these issues. However, many of these recommendations lacked follow-up implementation, allowing the damage of stagnant funding and outdated policies to persist. Here, we analyze nine reports published since the beginning of 2012 and consolidate over 250 suggestions into eight consensus recommendations made by the majority of the reports. We then propose how to implement these consensus recommendations, and we identify critical issues, such as improving workforce diversity and stakeholder interactions, on which the community has yet to achieve consensus.
Quantification and real-time tracking of RNA in live cells using Sticky-flares
Authors: Briley William E. , Bondy Madison H. , Randeria Pratik S. , Dupper Torin J. , Mirkin Chad A.
Published: July 2015

Significance

Proper function of RNA is critical to the health and maintenance of a cell, and its misregulation plays a critical role in the development of many disorders. To date, the ability to study RNA has been severely limited; many analytical techniques focus only on quantifying expression levels of transcripts and are not capable of reporting on intracellular localization, which has emerged as a critical component of RNA function. Similarly, techniques capable of probing RNA localization only offer snapshots in fixed cells. Herein we introduce a novel nanoconjugate, termed the Sticky-flare, capable of reporting on both of these critical components in live cells, thereby gaining a more complete picture or RNA function than any analytical technique to date.
A genetic basis of variation in eccrine sweat gland and hair follicle density
Authors: Kamberov Yana G. , Karlsson Elinor K. , Kamberova Gerda L. , Lieberman Daniel E. , Sabeti Pardis C. , Morgan Bruce A. , Tabin Clifford J.
Published: July 2015

Significance

Humans have the highest density of eccrine sweat glands of any mammal. Alongside hair follicles, eccrine glands are found throughout human skin and are indispensible for thermoregulation. Despite their importance, little is known about the biological factors that control eccrine gland formation and density. We investigated the genetic basis for the regulation of eccrine gland density in mice and find that eccrine gland and hair follicle densities are inversely regulated by the transcription factor En1. This work uncovers a previously unidentified biological factor that specifically promotes the development of eccrine glands when these organs are interspersed with hair follicles, and has the potential to inform efforts to elucidate the genetic basis for the evolution of increased eccrine gland density in humans.
Hole hopping through tyrosine/tryptophan chains protects proteins from oxidative damage
Authors: Gray Harry B. , Winkler Jay R.
Published: July 2015

Significance

Proteins and enzymes are susceptible to oxidative damage and inactivation from reactive oxygen and nitrogen species formed as a consequence of oxidative stress. They also are at risk from oxidizing intermediates formed during enzymatic turnover. A survey of the protein structural database has revealed that one third of structurally characterized proteins contain chains of redox-active tyrosine and tryptophan residues. These chains can protect proteins from damage by transferring oxidizing equivalents away from critical active site regions and delivering them to surface sites for scavenging.
CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts
Authors: Greenblatt Matthew B. , Park Kwang Hwan , Oh Hwanhee , Kim Jung-Min , Shin Dong Yeon , Lee Jae Myun , Lee Jin Woo , Singh Anju , Lee Ki-young , Hu Dorothy , Xiao Changchun , Charles Julia F. , Penninger Josef M. , Lotinun Sutada , Baron Roland , Ghosh Sankar , Shim Jae-Hyuck
Published: July 2015

Physiological bone remodeling requires that bone formation by osteoblasts be tightly coupled to bone resorption by osteoclasts. However, relatively little is understood about how this coupling is regulated. Here, we demonstrate that modulation of NF-κB signaling in osteoclasts via a novel activity of charged multivesicular body protein 5 (CHMP5) is a key determinant of systemic rates of bone turnover. A conditional deletion of CHMP5 in osteoclasts leads to increased bone resorption by osteoclasts coupled with exuberant bone formation by osteoblasts, resembling an early onset, polyostotic form of human Paget’s disease of bone (PDB). These phenotypes are reversed by haploinsufficiency for Rank, as well as by antiresorptive treatments, including alendronate, zolendronate, and OPG-Fc. Accordingly, CHMP5-deficient osteoclasts display increased RANKL-induced NF-κB activation and osteoclast differentiation. Biochemical analysis demonstrated that CHMP5 cooperates with the PDB genetic risk factor valosin-containing protein (VCP/p97) to stabilize the inhibitor of NF-κBα (IκBα), down-regulating ubiquitination of IκBα via the deubiquitinating enzyme USP15. Thus, CHMP5 tunes NF-κB signaling downstream of RANK in osteoclasts to dampen osteoclast differentiation, osteoblast coupling and bone turnover rates, and disruption of CHMP5 activity results in a PDB-like skeletal disorder.
Efficacy of Biofumigation with Brassica carinata Commercial Pellets (BioFence) to Control Vegetative and Reproductive Structures of Phytophthora cinnamomi
Authors: Morales-Rodríguez C. , Vettraino A. M. , Vannini A.
Published: July 2015

The efficacy of biofumigation with Brassica carinata pellets (BioFence) to control vegetative and reproductive structures of Phytophthora cinnamomi was investigated in vitro at different doses and temperatures. Biofumigation was effective in inhibiting mycelial growth (culture diameter) and chlamydospore and zoospore germination, and was lethal at 24 mg of pellet per plate (approximately 0.4 mg/liter). The 50% effective concentration values showed that efficacy of B. carinata pellets in inhibiting or killing the vegetative and reproductive structures of P. cinnamomi was maximum at 15°C and decreased as temperature rose to 25°C. However, the fungicide effect was independent of the temperature. In vivo biofumigation of Quercus cerris seedlings with BioFence confirmed efficacy by reducing the inoculum density (CFU/g) of P. cinnamomi, thus protecting the host from root infection. The use of BioFence provides an alternative to synthetic pesticides to control P. cinnamomi within disease management programs in agroforestry systems.
Overexpression of OsPGIP1 Enhances Rice Resistance to Sheath Blight
Authors: Chen X. J. , Chen Y. , Zhang L. N. , Xu B. , Zhang J. H. , Chen Z. X. , Tong Y. H. , Zuo S. M. , Xu J. Y.
Published: July 2015

Rice sheath blight (SB), caused by necrotrophic pathogen Rhizoctonia solani, is one of the most destructive rice diseases, and no major resistance genes are available. Polygalacturonase-inhibiting proteins (PGIP) are extracellular leucine-rich repeat proteins and play important roles in plant defense against different pathogenic fungi by counteracting secreted fungal polygalacturonases (PG). However, the role of PGIP in conferring resistance to rice SB remains to be thoroughly investigated. Here, we showed that OsPGIP1 is capable of inhibiting PG derived from R. solani. Our real-time reverse-transcription polymerase chain reaction results indicated that resistant rice ‘YSBR1’ and ‘Jasmine 85’ express significantly higher levels of OsPGIP1 than susceptible ‘Lemont’. Our results also show that OsPGIP1 is most highly expressed at the late tillering stage in the sheath of YSBR1, coinciding with the critical stage of SB development in field. More importantly, the OsPGIP1 level is highly elevated by inoculation with R. solani in resistant cultivars but not in susceptible Lemont. Overexpression of OsPGIP1 significantly increased rice resistance to SB and inhibited tissue degradation caused by R. solani-secreted PG. Furthermore, OsPGIP1 overexpression did not affect rice agronomic traits or yield components. Together, our results not only demonstrate the important role of OsPGIP1 in combatting the rice SB disease but also provide a new avenue to the improvement of rice SB resistance by manipulating an endogenous gene.
High Temperature Enhances the Resistance of Cultivated African Rice, Oryza glaberrima, to Bacterial Blight
Authors: Dossa Gerbert Sylvestre , Oliva Ricardo , Maiss Edgar , Vera Cruz Casiana , Wydra Kerstin
Published: July 2015

Rice bacterial blight (BB) is caused by Xanthomonas oryzae pv. oryzae and is responsible for substantial yield loss worldwide. Host resistance remains the most feasible control measure. However, pathogen variability leads to the failure of certain resistance genes to control the disease, and climate change with high amplitudes of heat predisposes the host plant to pathogen invasion. Due to pressure in natural selection, landrace species often carry a wide range of unique traits conferring tolerance of stress. Therefore, exploring their genetic background for host resistance could enable the identification of broad-spectrum resistance to combined abiotic and biotic stresses. Nineteen Oryza glaberrima accessions and O. sativa rice variety SUPA were evaluated for BB resistance under high temperature (35 and 31°C day and night, respectively) using 14 X. oryzae pv. oryzae strains originated from the Philippines. Under normal temperature, most of the accessions showed resistance to 9 strains (64.3%) and accession TOG6007 showed broad-spectrum resistance to 12 strains (85.7%). Under high temperature, most accessions showed a reduction in BB disease, whereas, accession TOG5620 showed disease reduction from all the X. oryzae pv. oryzae strains under high temperature. Molecular characterization using gene-based and linked markers for BB resistance genes Xa4, xa5, Xa7, xa13, and Xa21 revealed the susceptible alleles of Xa4, xa5, xa13, and Xa21 in O. glaberrima. However, no allele of Xa7 was detected among O. glaberrima accessions. Our results suggest that O. glaberrima accessions contain a BB resistance different from the Xa gene type. Genome-wide association mapping could be used to identify quantitative trait loci that are associated with BB resistance or combined BB resistance and high-temperature tolerance.
Bean common mosaic virus Isolate Exhibits a Novel Pathogenicity Profile in Common Bean, Overcoming the bc-3 Resistance Allele Coding for the Mutated eIF4E Translation Initiation Factor
Authors: Feng Xue , Myers James R. , Karasev Alexander V.
Published: July 2015

Resistance against Bean common mosaic virus (BCMV) in Phaseolus vulgaris is governed by six recessive resistance alleles at four loci. One of these alleles, bc-3, is able to protect P. vulgaris against all BCMV strains and against other potyviruses; bc-3 was identified as the eIF4E allele carrying mutated eukaryotic translation initiation factor gene. Here, we characterized a novel BCMV isolate 1755a that was able to overcome bc-2 and bc-3 alleles in common bean. Thus, it displayed a novel pattern of interactions with resistance genes in P. vulgaris, and was assigned to a new pathogroup, PG-VIII. The IVT7214 cultivar supporting the replication of BCMV-1755a was found to have the intact homozygous bc-3 cleaved amplified polymorphic sequences marker and corresponding mutations in the eIF4E allele that confer resistance to BCMV isolates from all other pathogroups as well as to other potyviruses. The VPg protein of 1755a had seven amino acid substitutions relative to VPgs of other BCMV isolates unable to overcome bc-3. The 1755a genome was found to be a recombinant between NL1, US1 (both PG-I), and a yet unknown BCMV strain. Analysis of the recombination patterns in the genomes of NL1 and US1 (PG-I), NY15P (PG-V), US10 and RU1-OR (PG-VII), and 1755a (PG-VIII), indicated that P1/HC-Pro cistrons of BCMV strains may interact with most resistance genes. This is the first report of a BCMV isolate able to overcome the bc-3 resistance allele, suggesting that the virus has evolved mechanisms to overcome multiple resistance genes available in common bean.
Ketamine Affects In Vitro Differentiation of Monocyte into Immature Dendritic Cells
Authors: Laudanski Krzysztof , Qing Meng , Oszkiel Hanna , Zawadka Mateusz , Lapko Natalia , Nowak Zbigniew , Worthen George S.
Published: July 2015

AbstractAbstract

At 10 μg/ml and higher concentrations, ketamine diminished expression of CD1a on interleukin-4 granulocyte–monocyte colony-stimulating factor–stimulated monocytes and retarded both their ability to process DQ ovalbumin and mixed lymphocyte reaction stimulation. The phagocytic abilities of interleukin-4 granulocyte–monocyte colony-stimulating factor–differentiated monocytes were not changed by ketamine.

Background:

Monocytes (MOs) have the unique ability to differentiate into immature dendritic cells (iDCs) (MO→iDC) under the influence of interleukin-4 and granulocyte–monocyte colony-stimulating factor (IL-4&GM-CSF). In this study, the authors investigated the influence of ketamine on the process of MO→iDC.

Methods:

iDCs were cultured from MO obtained from 36 subjects in the presence of IL-4 and GM-CSF and ketamine at 100, 10, and 1 μg/ml for 5 days. In some of the experiments, the authors used nonspecific N-methyl-d-aspartate (NMDA) receptor antagonist MK-801, NMDA, or a neutralizing antibody for transforming growth factor β (TGFβ). The expression of surface markers and functional assays were used to assess the effect of ketamine on IL-4&GM-CSF-stimulated MO. IL-4&GM-CSF-stimulated MO’s supernatants were assessed for cytokine levels.

Results:

Ketamine at 10 μg/ml, and higher concentrations, diminished the expression of CD1a on IL-4&GM-CSF-stimulated MO and retarded both their ability to process DQ ovalbumin and mixed lymphocyte reaction stimulation. The addition of ketamine to IL-4&GM-CSF-differentiated MO resulted in the persistent expression of CD14 and unchanged expression of CD86 and CD206. The phagocytic abilities of IL-4&GM-CSF-differentiated MO were not changed by ketamine. MK-801, a nonselective NMDA agonist, mimicked ketamine’s effect on MO→iDC differentiation. Adding exogenous NMDA to IL-4&GM-CSF-stimulated MO in the presence of ketamine partially restored the level of CD1a+. TGFβ was elevated in supernatants of IL-4&GM-CSF-stimulated MO in the presence of ketamine. Adding neutralizing TGFβ antibody or TGFβR1 blocker (SB431542) resulted in the full recovery of MO→iDC, despite the presence of ketamine.

Conclusions:

Ketamine diminishes the process of MO→iDC in vitro. This is mediated via NMDA-dependent mechanisms and TGFβ.
Erythema Multiforme Associated With Misoprostol: A Case Report
Authors: Sahraei Zahra , Mirabzadeh Mehran , Eshraghi Azadeh
Published: July 2015

A 33-year-old healthy woman at 6 weeks of gestation without any underlying disease developed erythema multiforme (EM) after misoprostol. She had no history of herpes simplex virus infection and drug allergy to nonsteroidal anti-inflammatory drugs and antibiotic agents. Medical abortion was performed at 6 weeks' gestation. Later day, the patient developed oral lesions as several white bullae lesions in her buccal mucosa and hyperkeratotic lip plaques with mild pain. Then, lesions resolved within approximately 3 weeks. Microscopic finding of oral biopsy from beneath the tongue and lesions was performed. The result was consistent with erosive mucosa with granulation tissue formation and acute inflammation in favor of EM. This is the case report of probable misoprostol-induced EM. Because EM may produce in skin as a Stevens–Johnson syndrome in subsequent attack, monitoring of this adverse drug reaction should be considered for proper management and follow-up.
Safety and Efficacy of Dexmedetomidine as a Sedative Agent for Performing Awake Intubation: A Meta-analysis
Authors: Zhou Luo-Jing , Fang Xiang-Zhi , Gao Ju , Zhangm Yang , Tao Li-Jian
Published: July 2015

To compare the efficacy and safety of dexmedetomidine with other alternative sedative agents used for performing awake intubation. We conducted a meta-analysis of randomized controlled trials (RCTs) that compared the effects of dexmedetomidine with other alternative sedative agents used during awake intubation. The biomedical databases PubMed, Science Direct, and the Cochrane Library were searched for relevant RCTs with no restriction on the language of publication. The efficacy (level of sedation, success rate for intubation at the first attempt, intubation time, intubation conditions, and patient satisfaction) and safety (incidence of hypertension, hypotension, tachycardia, bradycardia, hypoxia, postsurgical memory, hoarseness, and sore throat) were assessed. Thirteen RCTs with a combined subject population of 591 patients came within the purview of this meta-analysis. Use of dexmedetomidine was associated with a higher Ramsay sedation scale score [mean difference (MD): 1.02, 95% confidence interval (CI), 0.77–1.28, P < 0.00001], vocal cord movement score (MD = 0.72, 95% CI, 0.20–1.24, P = 0.007), coughing scores (MD = 0.66, 95% CI, 0.10–1.22, P = 0.02), limb movement scores (MD = 0.69, 95% CI, 0.47–0.91, P < 0.00001); increased risk of bradycardia [relative risk (RR): 3.03, 95% CI, 1.38–6.68, P = 0.006] and hypotension (RR: 2.87, 95% CI, 1.44–5.75, P = 0.003); and lower risk of hypoxia (RR: 0.32, 95% CI, 0.15–0.70; P = 0.004) and postsurgical memory (RR: 0.50, 95% CI, 0.35–0.72, P = 0.0002). As indicated by our results, dexmedetomidine appears to be an effective and well-tolerated agent for performing awake intubation. Its use was associated with better intubation conditions, preservation of airway patency, and reduced recall of intubation, as compared with the traditional sedative agents. The risk of bradycardia and hypotension was significantly higher with dexmedetomidine as compared with that with other sedatives. However, these were easily managed with atropine and vasoactive agents.
Effectiveness of Enteral Versus Oral Nutrition With a Medium‐Chain Triglyceride Formula to Prevent Malnutrition and Growth Impairment in Infants With Biliary Atresia
Authors: Macías‐Rosales Rocío , Larrosa‐Haro Alfredo , Ortíz‐Gabriel Genaro , Trujillo‐Hernández Benjamín
Published: July 2015

Objectives:

The aim of this study was to compare the effectiveness of oral (PO) versus enteral nutrition (EN) medium‐chain triglyceride (MCT) containing–formula to prevent malnutrition and growth impairment in infants with biliary atresia (BA) waiting for a liver transplant.

Methods:

A total of 15 infants, 3 to 9 months old with BA were included. They were randomly assigned to either PO or EN. For 12 weeks, both groups received an MCT formula fortified with glucose polymers and corn oil to reach a caloric density between 0.8 and 1 kcal/mL. The formula given to the PO group was administered ad libitum and that given via EN was infused through a nasogastric tube to reach 140% of the energy intake recommended by the Dietary Recommended Intake guidelines. Protein intake was adjusted to 4 to 5 g/kg present weight. Outcome variables were growth and nutritional status evaluated periodically by anthropometric indicators. Biochemical and hematological variables were evaluated through the study.

Results:

Baseline clinical, nutritional, biochemical, and hematological variables showed no differences between the study groups. Baseline length/age was <−2 SD in 10 of the 15 patients; in the PO group, it fell <−3 SD, whereas in the EN group, it remained stable. Head circumference z score dropped 0.6 SD in the PO group, whereas in the EN group it remained stable. Triceps skinfold values improved in the infants taking EN, P < 0.001. The frequency of adverse effects—respiratory infection and diarrhea—was higher in the EN group. No biochemical or hematological differences were observed between the study groups throughout the study.

Conclusions:

A 12‐week EN trial with an MCT‐fortified formula prevented malnutrition and growth impairment in infants with BA waiting for a liver transplant.
Small Bowel Bacterial Overgrowth in Children
Authors: Sieczkowska Agnieszka , Landowski Piotr , Kamińska Barbara , Lifschitz Carlos
Published: July 2015

Objectives:

The aim of study was to perform a comprehensive review of the pathogenesis, available diagnostic procedures, prevalence, clinical manifestations, and consequences of small bowel bacterial overgrowth (SBBO) as well as treatment options in the pediatric population.

Methods:

A literature search including MEDLINE, PubMed, and Web of Science databases was performed.

Results:

SBBO is found in a variety of childhood conditions in which the normal homeostatic mechanisms restricting bacterial colonization in the small bowel are disturbed by congenital or acquired anatomical abnormalities, diminished gastric acid secretion, congenital alteration of intestinal motility or acquired small bowel diseases, or other chronic disorders including primary or acquired immunodeficiency. Data show that SBBO may be an underrecognized cause of pediatric morbidity. Although several diagnostic tests for SBBO determination are available, each has its drawbacks and limitations. Indeed, there is still no “criterion standard” for SBBO diagnosis in the pediatric population. Owing to lack of established guidelines and few published interventional studies that assess the effectiveness of SBBO therapy, treatment of children with SBBO remains empiric and comprises antibiotic or probiotic therapy.

Conclusions:

Further research is needed to determine the clinical impact of SBBO and to establish diagnostic and therapeutic guidelines applicable to children.
The analysis of clonal expansions in normal and autoimmune B cell repertoires
Authors: Hershberg Uri , Luning Prak Eline T.
Published: July 2015

Clones are the fundamental building blocks of immune repertoires. The number of different clones relates to the diversity of the repertoire, whereas their size and sequence diversity are linked to selective pressures. Selective pressures act both between clones and within different sequence variants of a clone. Understanding how clonal selection shapes the immune repertoire is one of the most basic questions in all of immunology. But how are individual clones defined? Here we discuss different approaches for defining clones, starting with how antibodies are diversified during different stages of B cell development. Next, we discuss how clones are defined using different experimental methods. We focus on high-throughput sequencing datasets, and the computational challenges and opportunities that these data have for mining the antibody repertoire landscape. We discuss methods that visualize sequence variants within the same clone and allow us to consider collections of shared mutations to determine which sequences share a common ancestry. Finally, we comment on features of frequently encountered expanded B cell clones that may be of particular interest in the setting of autoimmunity and other chronic conditions.
Assigning and visualizing germline genes in antibody repertoires
Authors: Frost Simon D. W. , Murrell Ben , Hossain A. S. Md. Mukarram , Silverman Gregg J. , Pond Sergei L. Kosakovsky
Published: July 2015

Identifying the germline genes involved in immunoglobulin rearrangements is an essential first step in the analysis of antibody repertoires. Based on our prior work in analysing diverse recombinant viruses, we present IgSCUEAL (Immunoglobulin Subtype Classification Using Evolutionary ALgorithms), a phylogenetic approach to assign V and J regions of immunoglobulin sequences to their corresponding germline alleles, with D regions assigned using a simple pairwise alignment algorithm. We also develop an interactive web application for viewing the results, allowing the user to explore the frequency distribution of sequence assignments and CDR3 region length statistics, which is useful for summarizing repertoires, as well as a detailed viewer of rearrangements and region alignments for individual query sequences. We demonstrate the accuracy and utility of our method compared with sequence similarity-based approaches and other non-phylogenetic model-based approaches, using both simulated data and a set of evaluation datasets of human immunoglobulin heavy chain sequences. IgSCUEAL demonstrates the highest accuracy of V and J assignment amongst existing approaches, even when the reassorted sequence is highly mutated, and can successfully cluster sequences on the basis of shared V/J germline alleles.
Trade-offs in antibody repertoires to complex antigens
Authors: Childs Lauren M. , Baskerville Edward B. , Cobey Sarah
Published: July 2015

Pathogens vary in their antigenic complexity. While some pathogens such as measles present a few relatively invariant targets to the immune system, others such as malaria display considerable antigenic diversity. How the immune response copes in the presence of multiple antigens, and whether a trade-off exists between the breadth and efficacy of antibody (Ab)-mediated immune responses, are unsolved problems. We present a theoretical model of affinity maturation of B-cell receptors (BCRs) during a primary infection and examine how variation in the number of accessible antigenic sites alters the Ab repertoire. Naive B cells with randomly generated receptor sequences initiate the germinal centre (GC) reaction. The binding affinity of a BCR to an antigen is quantified via a genotype–phenotype map, based on a random energy landscape, that combines local and distant interactions between residues. In the presence of numerous antigens or epitopes, B-cell clones with different specificities compete for stimulation during rounds of mutation within GCs. We find that the availability of many epitopes reduces the affinity and relative breadth of the Ab repertoire. Despite the stochasticity of somatic hypermutation, patterns of immunodominance are strongly shaped by chance selection of naive B cells with specificities for particular epitopes. Our model provides a mechanistic basis for the diversity of Ab repertoires and the evolutionary advantage of antigenically complex pathogens.
Region-specific diversification of the highly virulent serotype 1 Streptococcus pneumoniae
Authors: Cornick Jennifer E. , Chaguza Chrispin , Harris Simon R. , Yalcin Feyruz , Senghore Madikay , Kiran Anmol M. , Govindpershad Shanil , Ousmane Sani , Plessis Mignon Du , Pluschke Gerd , Ebruke Chinelo , McGee Lesley , Sigaùque Beutel , Collard Jean-Marc , Antonio Martin , von Gottberg Anne , French Neil , Klugman Keith P. , Heyderman Robert S. , Bentley Stephen D. , Everett Dean B. ,   for the PAGe Consortium
Published: July 2015

Serotype 1 Streptococcus pneumoniae is a leading cause of invasive pneumococcal disease (IPD) worldwide, with the highest burden in developing countries. We report the whole-genome sequencing analysis of 448 serotype 1 isolates from 27 countries worldwide (including 11 in Africa). The global serotype 1 population shows a strong phylogeographic structure at the continental level, and within Africa there is further region-specific structure. Our results demonstrate that region-specific diversification within Africa has been driven by limited cross-region transfer events, genetic recombination and antimicrobial selective pressure. Clonal replacement of the dominant serotype 1 clones circulating within regions is uncommon; however, here we report on the accessory gene content that has contributed to a rare clonal replacement event of ST3081 with ST618 as the dominant cause of IPD in the Gambia.
Unearthing the microbial ecology of soil carbon cycling with DNA-SIP
Authors: Pepe-Ranney Charles , Campbell Ashley N , Koechli Chantal , Berthrong Sean , Buckley Daniel H
Published: July 2015

Introductory Paragraph

We explored the microbial contributions to decomposition using a sophisticated approach to DNA Stable Isotope Probing (SIP). Our experiment evaluated the dynamics and ecological characteristics of functionally defined microbial groups that metabolize labile and structural C in soils. We added to soil a complex amendment representing plant derived organic matter substituted with either13C-xylose or13C-cellulose to represent labile and structural C pools derived from abundant components of plant biomass. We found evidence for13C-incorporation into DNA from13C-xylose and13C-cellulose in 49 and 63 operational taxonomic units (OTUs), respectively. The types of microorganisms that assimilated13C in the13C-xylose treatment changed over time being predominantlyFirmicutesat day 1 followed byBacteroidetesat day 3 and thenActinobacteriaat day 7. These13C-labeling dynamics suggest labile C traveled through different trophic levels. In contrast, microorganisms generally metabolized cellulose-C after 14 days and did not change to the same extent in phylogenetic composition over time. Microorganisms that metabolized cellulose-C belonged to poorly characterized but cosmopolitan soil lineages includingVerrucomicrobia,ChloroflexiandPlanctomycetes.We show that microbial life history traits are likely to constrain the diversity of microorganisms that participate in the soil C-cycle.