bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and characterization of synthetic fungal-bacterial consortia for direct production of isobutanol from cellulosic biomass
Authors: Minty Jeremy J. , Singer Marc E. , Scholz Scott A. , Bae Chang-Hoon , Ahn Jung-Ho , Foster Clifton E. , Liao James C. , Lin Xiaoxia Nina
Published: August 2013

Synergistic microbial communities are ubiquitous in nature and exhibit appealing features, such as sophisticated metabolic capabilities and robustness. This has inspired fast-growing interest in engineering synthetic microbial consortia for biotechnology development. However, there are relatively few reports of their use in real-world applications, and achieving population stability and regulation has proven to be challenging. In this work, we bridge ecology theory with engineering principles to develop robust synthetic fungal-bacterial consortia for efficient biosynthesis of valuable products from lignocellulosic feedstocks. The required biological functions are divided between two specialists: the fungus
Trichoderma reesei
, which secretes cellulase enzymes to hydrolyze lignocellulosic biomass into soluble saccharides, and the bacterium
Escherichia coli
, which metabolizes soluble saccharides into desired products. We developed and experimentally validated a comprehensive mathematical model for
T. reesei
/
E. coli
consortia, providing insights on key determinants of the system’s performance. To illustrate the bioprocessing potential of this consortium, we demonstrate direct conversion of microcrystalline cellulose and pretreated corn stover to isobutanol. Without costly nutrient supplementation, we achieved titers up to 1.88 g/L and yields up to 62% of theoretical maximum. In addition, we show that cooperator–cheater dynamics within
T. reesei
/
E. coli
consortia lead to stable population equilibria and provide a mechanism for tuning composition. Although we offer isobutanol production as a proof-of-concept application, our modular system could be readily adapted for production of many other valuable biochemicals.
Synchronous interhemispheric Holocene climate trends in the tropical Andes
Authors: Polissar Pratigya J. , Abbott Mark B. , Wolfe Alexander P. , Vuille Mathias , Bezada Maximiliano
Published: August 2013

Holocene variations of tropical moisture balance have been ascribed to orbitally forced changes in solar insolation. If this model is correct, millennial-scale climate evolution should be antiphased between the northern and southern hemispheres, producing humid intervals in one hemisphere matched to aridity in the other. Here we show that Holocene climate trends were largely synchronous and in the same direction in the northern and southern hemisphere outer-tropical Andes, providing little support for the dominant role of insolation forcing in these regions. Today, sea-surface temperatures in the equatorial Pacific Ocean modulate rainfall variability in the outer tropical Andes of both hemispheres, and we suggest that this mechanism was pervasive throughout the Holocene. Our findings imply that oceanic forcing plays a larger role in regional South American climate than previously suspected, and that Pacific sea-surface temperatures have the capacity to induce abrupt and sustained shifts in Andean climate.
Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal–Hreidarsson syndrome
Authors: Deng Zhong , Glousker Galina , Molczan Aliah , Fox Alan J. , Lamm Noa , Dheekollu Jayaraju , Weizman Orr-El , Schertzer Michael , Wang Zhuo , Vladimirova Olga , Schug Jonathan , Aker Memet , Londoño-Vallejo Arturo , Kaestner Klaus H. , Lieberman Paul M. , Tzfati Yehuda
Published: August 2013

Significance

Telomeres protect the ends of eukaryotic chromosomes. Telomeres shorten with age and serve as a biological clock that limits cell proliferation. Excessive telomere shortening accelerates aging, but telomere elongation may facilitate cancer. We found inherited mutations in the regulator of telomere elongation helicase 1 (RTEL1), which cause Hoyeraal–Hreidarsson syndrome, a fatal disease characterized by accelerated telomere shortening, immunodeficiency, and developmental defects. Introducing a normal RTEL1 gene into affected cells prevented telomere shortening and extended their lifespan in culture. The telomere defects, genomic instability, and growth arrest observed in RTEL1-deficient cells help in our understanding the central roles of telomeres in aging and cancer.
Environmental productivity predicts migration, demographic, and linguistic patterns in prehistoric California
Authors: Codding Brian F. , Jones Terry L.
Published: August 2013

Global patterns of ethnolinguistic diversity vary tremendously. Some regions show very little variation even across vast expanses, whereas others exhibit dense mosaics of different languages spoken alongside one another. Compared with the rest of Native North America, prehistoric California exemplified the latter. Decades of linguistic, genetic, and archaeological research have produced detailed accounts of the migrations that aggregated to build California’s diverse ethnolinguistic mosaic, but there have been few have attempts to explain the process underpinning these migrations and why such a mosaic did not develop elsewhere. Here we show that environmental productivity predicts both the order of migration events and the population density recorded at contact. The earliest colonizers occupied the most suitable habitats along the coast, whereas subsequent Mid–Late Holocene migrants settled in more marginal habitats. Other Late Holocene patterns diverge from this trend, reflecting altered dynamics linked to food storage and increased sedentism. Through repeated migration events, incoming populations replaced resident populations occurring at lower densities in lower-productivity habitats, thereby resulting in the fragmentation of earlier groups and the development of one of the most diverse ethnolinguistic patterns in the Americas. Such a process may account for the distribution of ethnolinguistic diversity worldwide.
Protein kinase Cβ as a therapeutic target stabilizing blood–brain barrier disruption in experimental autoimmune encephalomyelitis
Authors: Lanz Tobias V. , Becker Simon , Osswald Matthias , Bittner Stefan , Schuhmann Michael K. , Opitz Christiane A. , Gaikwad Sadanand , Wiestler Benedikt , Litzenburger Ulrike M. , Sahm Felix , Ott Martina , Iwantscheff Simeon , Grabitz Carl , Mittelbronn Michel , von Deimling Andreas , Winkler Frank , Meuth Sven G. , Wick Wolfgang , Platten Michael
Published: August 2013

Disruption of the blood–brain barrier (BBB) is a hallmark of acute inflammatory lesions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis. This disruption may precede and facilitate the infiltration of encephalitogenic T cells. The signaling events that lead to this BBB disruption are incompletely understood but appear to involve dysregulation of tight-junction proteins such as claudins. Pharmacological interventions aiming at stabilizing the BBB in MS might have therapeutic potential. Here, we show that the orally available small molecule LY-317615, a synthetic bisindolylmaleimide and inhibitor of protein kinase Cβ, which is clinically under investigation for the treatment of cancer, suppresses the transmigration of activated T cells through an inflamed endothelial cell barrier, where it leads to the induction of the tight-junction molecules zona occludens-1, claudin 3, and claudin 5 and other pathways critically involved in transendothelial leukocyte migration. Treatment of mice with ongoing experimental autoimmune encephalomyelitis with LY-317615 ameliorates inflammation, demyelination, axonal damage, and clinical symptoms. Although LY-317615 dose-dependently suppresses T-cell proliferation and cytokine production independent of antigen specificity, its therapeutic effect is abrogated in a mouse model requiring pertussis toxin. This abrogation indicates that the anti-inflammatory and clinical efficacy is mainly mediated by stabilization of the BBB, thus suppressing the transmigration of encephalitogenic T cells. Collectively, our data suggest the involvement of endothelial protein kinase Cβ in stabilizing the BBB in autoimmune neuroinflammation and imply a therapeutic potential of BBB-targeting agents such as LY-317615 as therapeutic approaches for MS.
Establishing a hematopoietic genetic network through locus-specific integration of chromatin regulators
Authors: DeVilbiss Andrew W. , Boyer Meghan E. , Bresnick Emery H.
Published: August 2013

Significance

Broadly expressed enzymes commonly change chromatin structure and function. How ubiquitous chromatin regulators establish specialized patterns of gene activity is not understood. We identified an important link between a histone methyltransferase and a transcription factor (GATA-1) that controls red blood cell development. We found that distinct combinations of this enzyme and additional chromatin regulators are required for GATA-1 to control transcription at different genetic loci. The resulting regulatory “matrix” provides a conceptual framework for understanding how cell-restricted factors use broadly expressed chromatin regulators to confer specialized gene-expression patterns that control important biological processes.
Neural mechanisms of communicative innovation
Authors: Stolk Arjen , Verhagen Lennart , Schoffelen Jan-Mathijs , Oostenveld Robert , Blokpoel Mark , Hagoort Peter , van Rooij Iris , Toni Ivan
Published: August 2013

Human referential communication is often thought as coding–decoding a set of symbols, neglecting that establishing shared meanings requires a computational mechanism powerful enough to mutually negotiate them. Sharing the meaning of a novel symbol might rely on similar conceptual inferences across communicators or on statistical similarities in their sensorimotor behaviors. Using magnetoencephalography, we assess spectral, temporal, and spatial characteristics of neural activity evoked when people generate and understand novel shared symbols during live communicative interactions. Solving those communicative problems induced comparable changes in the spectral profile of neural activity of both communicators and addressees. This shared neuronal up-regulation was spatially localized to the right temporal lobe and the ventromedial prefrontal cortex and emerged already before the occurrence of a specific communicative problem. Communicative innovation relies on neuronal computations that are shared across generating and understanding novel shared symbols, operating over temporal scales independent from transient sensorimotor behavior.
Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes
Authors: Dean Samuel , Gould Matthew K. , Dewar Caroline E. , Schnaufer Achim C.
Published: August 2013

Viability of the tsetse fly-transmitted African trypanosome
Trypanosoma brucei
depends on maintenance and expression of its kinetoplast (kDNA), the mitochondrial genome of this parasite and a putative target for veterinary and human antitrypanosomatid drugs. However, the closely related animal pathogens
T. evansi
and
T. equiperdum
are transmitted independently of tsetse flies and survive without a functional kinetoplast for reasons that have remained unclear. Here, we provide definitive evidence that single amino acid changes in the nuclearly encoded F
1
F
O
–ATPase subunit γ can compensate for complete physical loss of kDNA in these parasites. Our results provide insight into the molecular mechanism of compensation for kDNA loss by showing F
O
-independent generation of the mitochondrial membrane potential with increased dependence on the ADP/ATP carrier. Our findings also suggest that, in the pathogenic bloodstream stage of
T. brucei
, the huge and energetically demanding apparatus required for kDNA maintenance and expression serves the production of a single F
1
F
O
–ATPase subunit. These results have important implications for drug discovery and our understanding of the evolution of these parasites.
Pathogenetic mechanisms of amyloid A amyloidosis
Authors: Simons J. Paul , Al-Shawi Raya , Ellmerich Stephan , Speck Ivana , Aslam Samrina , Hutchinson Winston L. , Mangione Palma P. , Disterer Petra , Gilbertson Janet A. , Hunt Toby , Millar David J. , Minogue Shane , Bodin Karl , Pepys Mark B. , Hawkins Philip N.
Published: August 2013

Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflammation before presenting, most commonly with renal involvement. Using dose-dependent, doxycycline-inducible transgenic expression of SAA in mice, we show that AA amyloid deposition can occur independently of inflammation and that the time before amyloid deposition is determined by the circulating SAA concentration. High level SAA expression induced amyloidosis in all mice after a short, slightly variable delay. SAA was rapidly incorporated into amyloid, acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest SAA overexpression occasionally produced amyloidosis after long delays and primed most mice for explosive amyloidosis when SAA production subsequently increased. Endogenous priming and bulk amyloid deposition are thus separable events, each sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with restoration of normal SAA production after doxycycline withdrawal. Reinduction of SAA overproduction revealed that, following amyloid regression, all mice were primed, especially for rapid glomerular amyloid deposition leading to renal failure, closely resembling the rapid onset of renal failure in clinical AA amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis rarely involves the heart, but amyloidotic SAA transgenic mice consistently had minor cardiac amyloid deposits, enabling us to extend to the heart the demonstrable efficacy of our unique antibody therapy for elimination of visceral amyloid.
Analysis of
Chlamydomonas
thiamin metabolism in vivo reveals riboswitch plasticity
Authors: Moulin Michael , Nguyen Ginnie T. D. T. , Scaife Mark A. , Smith Alison G. , Fitzpatrick Teresa B.
Published: August 2013

Thiamin (vitamin B
1
) is an essential micronutrient needed as a cofactor for many central metabolic enzymes. Animals must have thiamin in their diet, whereas bacteria, fungi, and plants can biosynthesize it de novo from the condensation of a thiazole and a pyrimidine moiety. Although the routes to biosynthesize these two heterocycles are not conserved in different organisms, in all cases exogenous thiamin represses expression of one or more of the biosynthetic pathway genes. One important mechanism for this control is via thiamin-pyrophosphate (TPP) riboswitches, regions of the mRNA to which TPP can bind directly, thus facilitating fine-tuning to maintain homeostasis. However, there is little information on how modulation of riboswitches affects thiamin metabolism in vivo. Here we use the green alga,
Chlamydomonas reinhardtii
, which regulates both thiazole and pyrimidine biosynthesis with riboswitches in the
THI4
(Thiamin 4) and
THIC
(Thiamin C) genes, respectively, to investigate this question. Our study reveals that regulation of thiamin metabolism is not the simple dogma of negative feedback control. Specifically, balancing the provision of both of the heterocycles of TPP appears to be an important requirement. Furthermore, we show that the
Chlamydomonas THIC
riboswitch is controlled by hydroxymethylpyrimidine pyrophosphate, as well as TPP, but with an identical alternative splicing mechanism. Similarly, the
THI4
gene is responsive to thiazole. The study not only provides insight into the plasticity of the TPP riboswitches but also shows that their maintenance is likely to be a consequence of evolutionary need as a function of the organisms’ environment and the particular pathway used.
Subtype-specific control of P2X receptor channel signaling by ATP and Mg
2
+
Authors: Li Mufeng , Silberberg Shai D. , Swartz Kenton J.
Published: August 2013

Significance

ATP is an important extracellular signal that activates P2X receptor channels. Although a large fraction of ATP is bound to divalent cations in vivo, the forms of ATP that activate P2X receptors are unknown. Here we show how the activity of homomeric P2X receptors is tuned by Mg
2+
in some subtypes by preventing activation by free ATP, and in others by binding to a distinct regulatory site. We also find that both regulatory mechanisms are disengaged in heteromeric channels to form a sensitive ATP signaling pathway. These fundamental properties of P2X receptors will be valuable for investigating their physiological functions.
Role of the ectonucleotidase NTPDase2 in taste bud function
Authors: Vandenbeuch Aurelie , Anderson Catherine B. , Parnes Jason , Enjyoji Keiichi , Robson Simon C. , Finger Thomas E. , Kinnamon Sue C.
Published: August 2013

Significance

ATP, a ubiquitous source of energy for all cells, also serves as an important messenger for intercellular communication. This role as a signal molecule is especially crucial for taste buds, which release ATP to trigger purinergic receptors on the taste nerves. Normally, the released ATP is degraded by a specific enzyme, nucleoside triphosphate diphosphohydrolase-2 (NTPDase2). We find that genetic elimination of NTPDase2 results in accumulation of ATP in extracellular space, thereby desensitizing the receptors on nerve fibers. The result is a loss of transmission of taste information from taste buds to the taste nerves. Disruption of taste function may be an unintended consequence of pharmaceutical agents now being developed to target purinergic receptors and enzymes as treatments for chronic pain and other illnesses.
Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats
Authors: Kim Eun Joo , Horovitz Omer , Pellman Blake A. , Tan Lancy Mimi , Li Qiuling , Richter-Levin Gal , Kim Jeansok J.
Published: August 2013

The periaqueductal gray (PAG) and amygdala are known to be important for defensive responses, and many contemporary fear-conditioning models present the PAG as downstream of the amygdala, directing the appropriate behavior (i.e., freezing or fleeing). However, empirical studies of this circuitry are inconsistent and warrant further examination. Hence, the present study investigated the functional relationship between the PAG and amygdala in two different settings, fear conditioning and naturalistic foraging, in rats. In fear conditioning, electrical stimulation of the dorsal PAG (dPAG) produced unconditional responses (URs) composed of brief activity bursts followed by freezing and 22-kHz ultrasonic vocalization. In contrast, stimulation of ventral PAG and the basolateral amygdalar complex (BLA) evoked freezing and/or ultrasonic vocalization. Whereas dPAG stimulation served as an effective unconditional stimulus for fear conditioning to tone and context conditional stimuli, neither ventral PAG nor BLA stimulation supported fear conditioning. The conditioning effect of dPAG, however, was abolished by inactivation of the BLA. In a foraging task, dPAG and BLA stimulation evoked only fleeing toward the nest. Amygdalar lesion/inactivation blocked the UR of dPAG stimulation, but dPAG lesions did not block the UR of BLA stimulation. Furthermore, in vivo recordings demonstrated that electrical priming of the dPAG can modulate plasticity of subiculum–BLA synapses, providing additional evidence that the amygdala is downstream of the dPAG. These results suggest that the dPAG conveys unconditional stimulus information to the BLA, which directs both innate and learned fear responses, and that brain stimulation-evoked behaviors are modulated by context.
Gene duplication in the major insecticide target site,Rdl, inDrosophila melanogaster
Authors: Remnant Emily J. , Good Robert T. , Schmidt Joshua M. , Lumb Christopher , Robin Charles , Daborn Phillip J. , Batterham Philip
Published: August 2013

TheResistance to Dieldringene,Rdl, encodes a GABA-gated chloride channel subunit that is targeted by cyclodiene and phenylpyrazole insecticides. The gene was first characterized inDrosophila melanogasterby genetic mapping of resistance to the cyclodiene dieldrin. The 4,000-fold resistance observed was due to a single amino acid replacement, Ala301to Ser. The equivalent change was subsequently identified inRdlorthologs of a large range of resistant insect species. Here, we report identification of a duplication at theRdllocus inD. melanogaster. The 113-kb duplication contains one WT copy ofRdland a second copy with two point mutations: an Ala301to Ser resistance mutation and Met360to Ile replacement. Individuals with this duplication exhibit intermediate dieldrin resistance compared with single copy Ser301homozygotes, reduced temperature sensitivity, and altered RNA editing associated with the resistant allele. Ectopic recombination betweenRootransposable elements is involved in generating this genomic rearrangement. The duplication phenotypes were confirmed by construction of a transgenic, artificial duplication integrating the 55.7-kbRdllocus with a Ser301change into an Ala301background. Gene duplications can contribute significantly to the evolution of insecticide resistance, most commonly by increasing the amount of gene product produced. Here however, duplication of theRdltarget site creates permanent heterozygosity, providing unique potential for adaptive mutations to accrue in one copy, without abolishing the endogenous role of an essential gene.
Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases
Authors: Jackson Walker S. , Borkowski Andrew W. , Watson Nicki E. , King Oliver D. , Faas Henryk , Jasanoff Alan , Lindquist Susan
Published: August 2013

In man, mutations in different regions of the prion protein (PrP) are associated with infectious neurodegenerative diseases that have remarkably different clinical signs and neuropathological lesions. To explore the roots of this phenomenon, we created a knock-in mouse model carrying the mutation associated with one of these diseases [Creutzfeldt–Jakob disease (CJD)] that was exactly analogous to a previous knock-in model of a different prion disease [fatal familial insomnia (FFI)]. Together with the WT parent, this created an allelic series of three lines, each expressing the same protein with a single amino acid difference, and with all native regulatory elements intact. The previously described FFI mice develop neuronal loss and intense reactive gliosis in the thalamus, as seen in humans with FFI. In contrast, CJD mice had the hallmark features of CJD, spongiosis and proteinase K-resistant PrP aggregates, initially developing in the hippocampus and cerebellum but absent from the thalamus. A molecular transmission barrier protected the mice from any infectious prion agents that might have been present in our mouse facility and allowed us to conclude that the diseases occurred spontaneously. Importantly, both models created agents that caused a transmissible neurodegenerative disease in WT mice. We conclude that single codon differences in a single gene in an otherwise normal genome can cause remarkably different neurodegenerative diseases and are sufficient to create distinct protein-based infectious elements.
Nonhuman primate model of schizophrenia using a noninvasive EEG method
Authors: Gil-da-Costa Ricardo , Stoner Gene R. , Fung Raynard , Albright Thomas D.
Published: August 2013

There is growing evidence that impaired sensory-processing significantly contributes to the cognitive deficits found in schizophrenia. For example, the mismatch negativity (MMN) and P3a event-related potentials (ERPs), neurophysiological indices of sensory and cognitive function, are reduced in schizophrenia patients and may be used as biomarkers of the disease. In agreement with glutamatergic theories of schizophrenia, NMDA antagonists, such as ketamine, elicit many symptoms of schizophrenia when administered to normal subjects, including reductions in the MMN and the P3a. We sought to develop a nonhuman primate (NHP) model of schizophrenia based on NMDA-receptor blockade using subanesthetic administration of ketamine. This provided neurophysiological measures of sensory and cognitive function that were directly comparable to those recorded from humans. We first developed methods that allowed recording of ERPs from humans and rhesus macaques and found homologous MMN and P3a ERPs during an auditory oddball paradigm. We then investigated the effect of ketamine on these ERPs in macaques. As found in humans with schizophrenia, as well as in normal subjects given ketamine, we observed a significant decrease in amplitude of both ERPs. Our findings suggest the potential of a pharmacologically induced model of schizophrenia in NHPs that can pave the way for EEG-guided investigations into cellular mechanisms and therapies. Furthermore, given the established link between these ERPs, the glutamatergic system, and deficits in other neuropsychiatric disorders, our model can be used to investigate a wide range of pathologies.
A nanoparticle formulation that selectively transfects metastatic tumors in mice
Authors: Yang Jian , Hendricks William , Liu Guosheng , McCaffery J. Michael , Kinzler Kenneth W. , Huso David L. , Vogelstein Bert , Zhou Shibin
Published: August 2013

Significance

To be effective, gene therapy vehicles must be able to deliver their therapeutic payloads to widely dispersed tumor lesions after systemic administration. We describe novel nanoparticles that provided a >16,000-fold increase in the ratio of tumor to nontumor cell delivery over conventional formulations. However, only a small fraction of neoplastic cells expressed the transgene, and the extent of delivery varied with the tumor cell line, tumor site, and host mouse strain used. Although our nanoparticles represent a technical advance, they also illustrate the challenges that remain before nonviral gene therapy can be applied to cancer patients.
Reproduction of the Blacktip Shark in the Gulf of Mexico
Authors: Baremore Ivy E. , Passerotti Michelle S.
Published: August 2013

Reproductive and age data were collected for Blacktip Sharks Carcharhinus limbatus in the Gulf of Mexico from fishery-dependent and -independent sources from 2006 to 2011 for stock assessment. A total of 757 Blacktip Sharks were sampled for reproductive analysis (399 females, 358 males), of which 741 were aged. Additional length and age data from a previous age and growth study on Blacktip Sharks in the Gulf of Mexico (207 females, 161 males) were incorporated into the size- and age-at-maturity analyses. The results indicated that Blacktip Sharks in the Gulf of Mexico have a synchronous, seasonal reproductive cycle and that females exhibit a biennial ovarian cycle. Male and female mating and parturition peaked from March to May. Length at 50% maturity was estimated to be 105.8 and 119.2 cm FL for males and females, respectively, while age at 50% maturity was calculated as 4.8 and 6.3 years. Near-term pups averaged 38 cm FL, and gestation was approximately 12 months. Litter size was 4.5 pups per female, and fecundity was found to increase with both maternal size and age. Maternal body size—but not age—had a positive influence on offspring fitness. This represents the first comprehensive reproductive study of Blacktip Sharks in the Gulf of Mexico.

Received October 1, 2012; accepted December 5, 2012
Variability in the Reproductive Biology of the Atlantic Sharpnose Shark in the Gulf of Mexico
Authors: Hoffmayer Eric R. , Driggers William B. , Jones Lisa M. , Hendon Jill M. , Sulikowski James A.
Published: August 2013

The reproductive biology of the Atlantic Sharpnose Shark Rhizoprionodon terraenovae in the Gulf of Mexico was investigated by examining 1,306 specimens (693 females, 613 males) collected from the Florida Keys to waters off Brownsville, Texas. The results of this study confirm the annual reproductive cycle established for this species; however, there was a significant amount of variability within the cycle. Ovulatory and postovulatory females were present from March to October, indicating that mating and ovulation were occurring over a more protracted period than previously described (e.g., May to July). The occurrence of postpartum females from April to September, the varying sizes of the embryos across several months, and the occurrence of mature spermatozoa in the testes of adults from March to November also corroborate the evidence of reproductive plasticity in this species. This observed variability in the reproductive cycle indicates that the Gulf of Mexico Atlantic Sharpnose Shark population is not completely synchronous in regards to mating, ovulation, and parturition, as a portion of the population is demonstrating reproductive asynchrony. Although the cause of this asynchrony remains unclear, it may be related to the environmental conditions of the Gulf of Mexico, which could provide water temperatures that are optimal for the reproduction of this species through much of the year (i.e., March to October), resulting in a protracted reproductive cycle. Given the results of the current study, the reproductive cycles of other carcharhinid species in this region should be examined in more detail to determine whether there is asynchrony in them as well, as this phenomenon could impact future management strategies.

Received October 26, 2012; accepted March 5, 2013
Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract
Authors: Ruane Darren , Brane Lucas , Reis Bernardo Sgarbi , Cheong Cheolho , Poles Jordan , Do Yoonkyung , Zhu Hongfa , Velinzon Klara , Choi Jae-Hoon , Studt Natalie , Mayer Lloyd , Lavelle Ed C. , Steinman Ralph M. , Mucida Daniel , Mehandru Saurabh
Published: August 2013

Developing efficacious vaccines against enteric diseases is a global challenge that requires a better understanding of cellular recruitment dynamics at the mucosal surfaces. The current paradigm of T cell homing to the gastrointestinal (GI) tract involves the induction of α4β7 and CCR9 by Peyer’s patch and mesenteric lymph node (MLN) dendritic cells (DCs) in a retinoic acid–dependent manner. This paradigm, however, cannot be reconciled with reports of GI T cell responses after intranasal (i.n.) delivery of antigens that do not directly target the GI lymphoid tissue. To explore alternative pathways of cellular migration, we have investigated the ability of DCs from mucosal and nonmucosal tissues to recruit lymphocytes to the GI tract. Unexpectedly, we found that lung DCs, like CD103+ MLN DCs, up-regulate the gut-homing integrin α4β7 in vitro and in vivo, and induce T cell migration to the GI tract in vivo. Consistent with a role for this pathway in generating mucosal immune responses, lung DC targeting by i.n. immunization induced protective immunity against enteric challenge with a highly pathogenic strain of Salmonella. The present report demonstrates novel functional evidence of mucosal cross talk mediated by DCs, which has the potential to inform the design of novel vaccines against mucosal pathogens.
DNA repair genes are selectively mutated in diffuse large B cell lymphomas
Authors: de Miranda Noel FCC , Peng Roujun , Georgiou Konstantinos , Wu Chenglin , Sörqvist Elin Falk , Berglund Mattias , Chen Longyun , Gao Zhibo , Lagerstedt Kristina , Lisboa Susana , Roos Fredrik , van Wezel Tom , Teixeira Manuel R. , Rosenquist Richard , Sundström Christer , Enblad Gunilla , Nilsson Mats , Zeng Yixin , Kipling David , Pan-Hammarström Qiang
Published: August 2013

DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis.
Sheaves on ℙ¹×ℙ¹, bigraded resolutions, and coadjoint orbits of loop groups
Authors: Bielawski Roger , Schwachhöfer Lorenz
Published: August 2013

We construct a canonical linear resolution of acyclic

1
1

-dimensional sheaves on

P

1

×

P

1

\mathbb {P}^1\times \mathbb {P}^1

and discuss the resulting natural Poisson structure.
RDAVIDWebService: a versatile R interface to DAVID
Authors: Fresno Cristóbal , Fernández Elmer A.
Published: August 2013

Summary: The RDAVIDWebService package provides a class-based interface from R programs/scripts to fully access/control the database for annotation, visualization and integrated discovery, without the need for human interaction on its Web site (http://david.abcc.ncifcrf.gov). The library enhances the database for annotation, visualization and integrated discovery capabilities for Gene Ontology analysis by means of GOstats-based direct acyclic graph conversion methods, in addition to the usual many-genes-to-many-terms visualization.

Availability and implementation: RDAVIDWebService is available as an R package from the Bioconductor project (www.bioconductor.org) and on the authors’ Web site (www.bdmg.com.ar) under GPL-2 license, subjected to the terms of use of DAVID (http://david.abcc.ncifcrf.gov/content.jsp?file=WS.html).

Contact: cfresno@bdmg.com.ar or efernandez@bdmg.com.ar
Impact of survey design changes on stock assessment advice: sea scallops
Authors: Smith Stephen J. , Hubley Brad
Published: August 2013

Smith, S. J., and Hubley, B. 2014. Impact of survey design changes on stock assessment advice: sea scallops. – ICES Journal of Marine Science, 71: 320–327. Annual surveys of marine resources are used to monitor changes in population composition and abundance. Improvements in the performance and coverage of these surveys can readily be evaluated for the surveys themselves but should also be considered in the context of the stock assessment models that use the estimates from these surveys. For those surveys based on a probability design, improvements in the probability design are usually evaluated with respect to the resultant increase in precision of the survey estimates. Survey precision estimates can be included in many stock assessment models as observation error, as long as the process error component of the model is also identified. Advice on catch levels for sea scallop populations (Placopecten magellanicus) around Nova Scotia is developed using a Bayesian state space assessment model in which both observation and process error terms have been defined. Information on survey estimates of precision are included in the observation error component of the assessment model and the impacts of changes in survey precision on the provision of advice can be evaluated in terms of reference points and management advice. The sensitivity of stock assessment advice to changes in the level of precision of survey estimates was evaluated for three scallop fisheries around Nova Scotia. The results indicated that the impact of the changes depended upon the degree of concurrence between the annual changes in biomass as observed from the survey and those predicted by the model.
Time-dependent 3D magnetohydrodynamic pulsar magnetospheres: oblique rotators
Authors: Tchekhovskoy Alexander , Spitkovsky Anatoly , Li Jason G.
Published: August 2013

The current state of the art in pulsar magnetosphere modelling assumes the force-free limit of magnetospheric plasma. This limit retains only partial information about plasma velocity and neglects plasma inertia and temperature. We carried out time-dependent 3D relativistic magnetohydrodynamic (MHD) simulations of oblique pulsar magnetospheres that improve upon force free by retaining the full plasma velocity information and capturing plasma heating in strong current layers. We find rather low levels of magnetospheric dissipation, with < 10 per cent of pulsar spin-down energy dissipated within a few light cylinder radii, and the MHD spin-down that is consistent with that in force free. While oblique magnetospheres are qualitatively similar to the rotating split-monopole force-free solution at large radii, we find substantial quantitative differences with the split-monopole, e.g., the luminosity of the pulsar wind is more equatorially concentrated than the split-monopole at high obliquities, and the flow velocity is modified by the emergence of reconnection flow directed into the current sheet.
Hypoglycemic and Antioxidative Effects of Instant Cooked Giant Embryonic Rice in High‐Fat‐Fed Mice
Authors: Chung Soo Im , Kim Tae Hyeong , Rico Catherine W. , Kang Mi Young
Published: August 2013

The effect of instant cooked rice made from giant embryo mutant or ordinary normal rice on the glucose metabolism and antioxidative defense system in mice under a high‐fat (HF) diet condition was investigated. The animals were randomly divided and given experimental diets for seven weeks: normal control diet, HF diet, and HF diet supplemented with instant normal white, normal brown, giant embryonic white, or giant embryonic brown rice. At the end of the experimental period, the HF mice showed a marked increase in the blood glucose level, insulin concentration, and plasma and erythrocyte lipid peroxidation and a significant decrease in the glycogen level relative to the control group. However, diet supplementation with instant cooked giant embryonic and normal brown rice counteracted this high‐fat‐induced hyperglycemia and oxidative stress through regulation of the glucose‐regulating and antioxidant enzyme activities. The giant embryonic brown rice was the most effective in improving the glucose metabolism and antioxidant defense status in mice under the HF diet condition. The results demonstrate that the giant embryo rice mutant may be useful in the development of instant cooked rice with strong hypoglycemic and antioxidative properties.
Horace Wells’ Demonstration of Nitrous Oxide in Boston
Authors: Haridas Rajesh P.
Published: August 2013

Horace Wells, a dentist in Hartford, Connecticut, first used nitrous oxide in dentistry in December 1844. A few weeks later he travelled to Boston, Massachusetts, to demonstrate to physicians and dentists the use of nitrous oxide in painful procedures. Wells’ unsuccessful demonstration of nitrous oxide for the extraction of a tooth is well known, but other details of this trip are poorly understood. A description of Wells’ visit to Boston was compiled using information from 21 statements and 5 newspaper notices. The precise date and location of Wells’ demonstration could not be determined. There is no primary evidence that Wells’ demonstration occurred in the surgical amphitheater (Ether Dome) at Massachusetts General Hospital. Wells’ demonstration of nitrous oxide probably occurred around the end of January 1845, in a public hall on Washington Street, Boston.
The consensus problem in networks with transmission delays
Authors: Atay Fatihcan M.
Published: August 2013

We study discrete- and continuous-time consensus problems on networks in the presence of distributed time delays. We focus on information transmission delays, as opposed to information processing delays, so that each node of the network compares its current state with the past states of its neighbours. We consider directed and weighted networks where the connection structure is described by a normalized Laplacian matrix and show that consensus is achieved if and only if the underlying graph contains a directed spanning tree. This statement holds independently of the transmission delays, which is in contrast to the case of processing delays. Furthermore, we calculate the consensus value explicitly, and show that it is determined by the history of the system over an interval of time, unlike the case of processing delays where the consensus value depends only on the initial state of the system at time zero. This provides the consensus algorithm with improved robustness against noise.
Feedback control of unstable periodic orbits in equivariant Hopf bifurcation problems
Authors: Postlethwaite C. M. , Brown G. , Silber M.
Published: August 2013

Symmetry-breaking Hopf bifurcation problems arise naturally in studies of pattern formation. These equivariant Hopf bifurcations may generically result in multiple solution branches bifurcating simultaneously from a fully symmetric equilibrium state. The equivariant Hopf bifurcation theorem classifies these solution branches in terms of their symmetries, which may involve a combination of spatial transformations and temporal shifts. In this paper, we exploit these spatio-temporal symmetries to design non-invasive feedback controls to select and stabilize a targeted solution branch, in the event that it bifurcates unstably. The approach is an extension of the Pyragas delayed feedback method, as it was developed for the generic subcritical Hopf bifurcation problem. Restrictions on the types of groups where the proposed method works are given. After addition of the appropriately optimized feedback term, we are able to compute the stability of the targeted solution using standard bifurcation theory, and give an account of the parameter regimes in which stabilization is possible. We conclude by demonstrating our results with a numerical example involving symmetrically coupled identical nonlinear oscillators.
Delayed feedback control of three diffusively coupled Stuart–Landau oscillators: a case study in equivariant Hopf bifurcation
Authors: Schneider Isabelle
Published: August 2013

The modest aim of this case study is the non-invasive and pattern-selective stabilization of discrete rotating waves (‘ponies on a merry-go-round’) in a triangle of diffusively coupled Stuart–Landau oscillators. We work in a setting of symmetry-breaking equivariant Hopf bifurcation. Stabilization is achieved by delayed feedback control of Pyragas type, adapted to the selected spatio-temporal symmetry pattern. Pyragas controllability depends on the parameters for the diffusion coupling, the complex control amplitude and phase, the uncontrolled super-/sub-criticality of the individual oscillators and their soft/hard spring characteristics. We mathematically derive explicit conditions for Pyragas control to succeed.
Mesoaciditoga lauensis gen. nov., sp. nov., a moderately thermoacidophilic member of the order Thermotogales from a deep-sea hydrothermal vent
Authors: Reysenbach Anna-Louise , Liu Yitai , Lindgren Annie R. , Wagner Isaac D. , Sislak Christine D. , Mets Anchelique , Schouten Stefan
Published: August 2013

A novel moderately thermophilic, heterotrophic bacterium was isolated from a deep-sea hydrothermal vent deposit from the Mariner field along the Eastern Lau Spreading Center of the south-western Pacific Ocean. Cells were short motile rods (about 0.4×0.8 µm) that occurred singly or in pairs and were surrounded by a sheath-like membrane or ‘toga’. The cells grew between 45 and 65 °C (optimum 57–60 °C) and at pH 4.1–6.0 (optimum pH 5.5–5.7) and grew optimally at 3 % (w/v) NaCl. The isolate grew on a range of carbon and proteinaceous substrates and reduced sulfur. The G+C content of the DNA was about 45 mol%. Phylogenetic analysis of the 16S rRNA gene sequence placed the new isolate as a deeply diverging lineage within the order

Thermotogales

. Based on the physiological, morphological and phylogenetic data, the isolate represents a novel species of a new genus with the proposed name Mesoaciditoga lauensis gen. nov., sp. nov. The type strain of Mesoaciditoga lauensis is cd-1655RT ( = DSM 25116T = OCM 1212T).
Enterococcus saccharolyticus subsp. taiwanensis subsp. nov., isolated from broccoli
Authors: Chen Yi-sheng , Lin Yu-hsuan , Pan Shwu-fen , Ji Si-hua , Chang Yu-chung , Yu Chi-rong , Liou Min-shiuan , Wu Hui-chung , Otoguro Misa , Yanagida Fujitoshi , Liao Chen-chung , Chiu Chi-ming , Huang Bi-qiang
Published: August 2013

A coccal strain isolated from fresh broccoli was initially identified asEnterococcus saccharolyticus; however, molecular identification and phenotypic traits did not support this identification. DNA–DNA hybridization with the type strain ofE. saccharolyticus(76.4 % relatedness), DNA G+C content (35.7 mol%), phylogenetic analysis based on 16S rRNA,pheSandrpoAgene sequences, rep-PCR fingerprinting and profiles of cellular fatty acids, whole-cell proteins and enzyme activities, together with carbohydrate metabolism characteristics, indicated that this strain is distinct and represents a novel subspecies, for which the nameEnterococcus saccharolyticussubsp.taiwanensissubsp. nov. is proposed. The type strain is 812T( = NBRC 109476T = BCRC 80575T). Furthermore, we present an emended description ofEnterococcus saccharolyticusand proposal ofEnterococcus saccharolyticussubsp.saccharolyticussubsp. nov. (type strain ATCC 43076T = CCUG 27643T = CCUG 33311T = CIP 103246T = DSM 20726T = JCM 8734T = LMG 11427T = NBRC 100493T = NCIMB 702594T).
Streptomyces yaanensis sp. nov., isolated from soil
Authors: Zheng Jimei , Zhang Xuefang , Xin Yuhua , Han Xiufang , Ni Shufan , Zhang Jianli
Published: August 2013

A novel actinomycete, designated Z4T, was isolated from soil in Yaan, Sichuan Province, south China. The taxonomic status of this strain was established using a polyphasic approach. The morphological and chemotaxonomic characteristics of the organism are typical of the members of the genusStreptomyces. Phylogenetic analysis based on the almost complete 16S rRNA gene sequence indicated that strain Z4Tbelonged to the genusStreptomyces, branching off next toStreptomyces durhamensisATCC 23194T(98.7 %),Streptomyces puniciscabieiKACC 20253T(98.7 %) andStreptomyces filipinensisATCC 23905T(98.6 %). However, DNA–DNA hybridization studies and phenotypic differences between strain Z4Tand closely related species of the genusStreptomycessuggested that strain Z4Trepresented a different genomic species. It is therefore proposed that Z4T( = CGMCC 4.7035T = KCTC 29111T) represents the type strain of a novel species of the genusStreptomyces, for which the nameStreptomycesyaanensissp. nov. is proposed.