bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Dose Radioactive Iodine Ablation Is Sufficient in Patients With Small Papillary Thyroid Cancer Having Minor Extrathyroidal Extension and Central Lymph Node Metastasis (T3 N1a)
Authors: Seo Minjung , Kim Yon Seon , Lee Jong Cheol , Han Myung Woul , Kim Eun Sook , Kim Kyung Bin , Park Seol Hoon
Published: August 2017

Purpose

The aim of this study was to evaluate the effectiveness of low-dose radioactive iodine (RAI) ablation in patients with small papillary thyroid cancer (PTC) exhibiting microscopic extrathyroidal extension (mETE) and central lymph node (CLN) metastasis.

Methods

Among patients who underwent RAI ablation between March 2007 and February 2014, those who had small PTCs (≤2 cm), as well as mETE and CLN metastasis (T3 N1a M0), were enrolled. Response to ablation and long-term outcomes were assessed and compared according to the administered RAI dose. Factors associated with unsuccessful ablation were also determined.

Results

A total of 180 patients were included in the study. Eighty-eight patients had been treated with 1110 MBq (low-dose group) and 92 with 2960 MBq (high-dose group) of RAI. There were no significant differences in the responses to ablation (P = 0.810) and long-term outcomes (P = 0.663) between both groups. Among all patients enrolled, 13 did not achieve successful ablation at long-term follow-up. Logistic regression found that a high ratio of metastatic nodes was a significant factor for predicting unsuccessful ablation.

Conclusions

Low-dose RAI ablation did not produce significantly different responses or long-term outcomes in patients with small PTCs exhibiting mETE and CLN metastasis. These findings suggest that low-dose ablation may be sufficient in this specific group of intermediate-risk patients, although careful selection is required for patients with a high ratio of metastatic nodes.
Small Hepatocellular Carcinoma With Low Tumor Marker Expression Benefits More From Anatomical Resection Than Tumors With Aggressive Biology
Authors: Jung Dong-Hwan , Hwang Shin , Lee Young-Joo , Kim Ki-Hun , Song Gi-Won , Ahn Chul-Soo , Moon Deok-Bog , Lee Sung-Gyu
Published: August 2017

Objective:

We assessed prognostic advantage of anatomical resection (AR) over nonanatomical resection (NAR) for hepatocellular carcinoma (HCC) according to multiplication of α-fetoprotein, des-γ-carboxyprothrombin, and tumor volume (ADV) scores.

Background:

Superiority of AR over NAR is debated. ADV score is surrogate marker of postresection prognosis for solitary HCC.

Methods:

This study included 1572 patients who underwent curative resection for solitary HCC of 2.0 to 5.0 cm between 2006 and 2014.

Results:

Preoperative patient profiles were not statistically different between AR and NAR groups. In 1324 naïve patients without preoperative treatment, AR group showed lower recurrence rates (P = 0.003) and higher patient survival rates (P = 0.012) than NAR group. AR group showed lower recurrence rates in patients with ADV ≤5 log (P ≤ 0.046). ADV scores >4 log and >3 log were independent risk factors for tumor recurrence and patient survival in treatment-naïve patients, respectively. In treatment-naïve group with preserved hepatic functional reserve, AR group showed lower recurrence rates in patients with ADV ≤4 log (P = 0.026). Absence of microvascular invasion also showed lower recurrence rates (P = 0.007) in AR group. In 248 patients with preoperative treatment, AR group showed lower recurrence rates (P = 0.001) and higher patient survival rates (P = 0.006). AR group showed lower recurrence rates in patients with ADV ≤4 log (P < 0.001) and higher survival rates in patients with ADV ≤5 log (P ≤ 0.043).

Conclusions:

Prognostic benefit of AR was evident in patients with ADV score ≤4 log or absence of microvascular invasion. Patients with less aggressive tumor biology benefit more from AR than NAR, thus being reasonably indicated for AR.
Characteristics of Effective Mentorship for Academic Surgeons
Authors: Cochran Amalia , Elder William B. , Neumayer Leigh A.
Published: August 2017

Objective:

The authors sought to describe characteristics of effective mentoring relationships in academic surgery based upon lived experiences of mid-career and senior female academic surgeons.

Background:

Prior qualitative work describes characteristics of successful mentoring relationships. However, no model exists of effective mentorship that is specific to academic surgery.

Methods:

The authors conducted in-depth interviews with mid-career and senior female US academic surgeons about the impact of mentoring on professional development during 2014 and 2015. Purposive selection aimed to maximize institutional, specialty, years in career, and racial diversity. Grounded theory method was used to generate a conceptual model of effective mentoring relationships. Data saturation occurred following 15 interviews.

Results:

Interviewees described the need for multiple mentors over time with each mentor addressing a unique domain. Interviewees suggested that mentees should seek mentors who will serve as strategic advisors, who will be unselfish, and who engage with diverse mentees.

Conclusions:

This study identified a need for multiple mentors across time and disciplines, and identified 3 key characteristics of effective mentoring relationships in academic surgery. Future work in this area should generate an operational definition of mentorship that supports quantitative evaluation of mentor and mentoring panel performance.
Delayed Onset Cranial Nerve Palsies After Endovascular Coil Embolization of Direct Carotid-Cavernous Fistulas
Authors: Bou Ghannam Alaa , Subramanian Prem S.
Published: August 2017

Background:

Late recurrence of visual symptoms associated with carotid-cavernous fistula (CCF), including diplopia, is uncommon and raises concern for new or recurrent fistula formation.

Methods:

We report 2 patients with traumatic CCFs, where cranial nerve paresis resolved after endovascular CCF treatment only to reappear years later.

Results:

No evidence of recurrent or new fistula formation was found. Both were treated successfully with strabismus surgery.

Conclusions:

Although the cause of delayed onset diplopia after successful treatment is still unknown, theories include late compression of cranial nerves within the cavernous sinus due to coil mass that can cause chronic ischemia, delayed inflammation due to a thrombophilic nidus created by the coil mass, or injury to the cranial nerves that manifests later due to decompensated strabismus.
Sea-ice induced growth decline in Arctic shrubs
Authors: Forchhammer Mads
Published: August 2017

Measures of increased tundra plant productivity have been associated with the accelerating retreat of the Arctic sea-ice. Emerging studies document opposite effects, advocating for a more complex relationship between the shrinking sea-ice and terrestrial plant productivity. I introduce an autoregressive plant growth model integrating effects of biological and climatic conditions for analysing individual ring-width growth time series. Using 128 specimens ofSalix arctica,S. glaucaandBetula nanasampled across Greenland to Svalbard, an overall negative effect of the retreating June sea-ice extent was found on the annual growth. The negative effect of the retreating June sea-ice was observed for younger individuals with large annual growth allocations and with little or no trade-off between previous and current year's growth.
Anatole Abragam. 15 December 1914 — 8 June 2011
Authors: Goldman Maurice
Published: August 2017

Anatole Abragam, a French physicist of Russian origin, made a profound and lasting impact on the field of magnetic resonance, both electronic and nuclear, through his discoveries, contributions and his eminent educational role. In nuclear magnetic resonance (NMR) especially, he brought to the field theoretical rigour and clarity. Many of the most distinguished scientists in the field consider themselves to be his students, and he is known by many as a ‘giant of magnetic resonance’. Among his main contributions are: theories of the spin Hamiltonian and of core polarization in electron paramagnetic resonance (EPR); the theory of perturbed angular correlations of radioactive emissions in condensed matter; a new theoretical formalism of spin relaxation; the invention of an Earth magnetometer; basic studies of spin temperature; dynamic nuclear polarization in solids and production of polarized targets; nuclear dipolar magnetic ordering studied both by NMR and by neutron diffraction; the discovery of nuclear pseudo-magnetism and its use for measuring the spin-dependent neutron–nucleus scattering amplitudes; and a new spectroscopic technique for muon spin rotation (
μ
SR).
Optimization of fermentation conditions for the production of curcumin by engineered
Escherichia coli
Authors: Couto Márcia R. , Rodrigues Joana L. , Rodrigues Lígia R.
Published: August 2017

Curcumin is a plant secondary metabolite with outstanding therapeutic effects. Therefore, there is a great interest in developing new strategies to produce this high-value compound in a cheaper and environmentally friendly way. Curcumin heterologous production in
Escherichia coli
using artificial biosynthetic pathways was previously demonstrated using synthetic biology approaches. However, the culturing conditions to produce this compound were not optimized and so far only a two-step fermentation process involving the exchange of culture medium allowed high concentrations of curcumin to be obtained, which limits its production at an industrial scale. In this study, the culturing conditions to produce curcumin were evaluated and optimized. In addition, it was concluded that
E. coli
BL21 allows higher concentrations of curcumin to be produced than
E. coli
K-12 strains. Different isopropyl β-
d
-thiogalactopyranoside concentrations, time of protein expression induction and substrate type and concentration were also evaluated. The highest curcumin production obtained was 959.3 µM (95.93% of per cent yield), which was 3.1-fold higher than the highest concentration previously reported. This concentration was obtained using a two-stage fermentation with lysogeny broth (LB) and M9. Moreover, terrific broth was also demonstrated to be a very interesting alternative medium to produce curcumin because it also led to high concentrations (817.7 µM). The use of this single fermentation medium represents an advantage at industrial scale and, although the final production is lower than that obtained with the LB–M9 combination, it leads to a significantly higher production of curcumin in the first 24 h of fermentation. This study allowed obtaining the highest concentrations of curcumin reported so far in a heterologous organism and is of interest for all of those working with the heterologous production of curcuminoids, other complex polyphenolic compounds or plant secondary metabolites.
AMP-activated protein kinase: a therapeutic target in intestinal diseases
Authors: Sun Xiaofei , Zhu Mei-Jun
Published: August 2017

Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a highly conserved energy sensor, has a crucial role in cardiovascular, neurodegenerative and inflammatory diseases, as well as in cancer and metabolic disorders. Accumulating studies have demonstrated that AMPK activation enhances paracellular junctions, nutrient transporters, autophagy and apoptosis, and suppresses inflammation and carcinogenesis in the intestine, indicating an essential role of AMPK in intestinal health. AMPK inactivation is an aetiological factor in intestinal dysfunctions. This review summarizes the favourable outcomes of AMPK activation on intestinal health, and discusses AMPK as a potential therapeutic target for intestinal diseases.
Synthesis of isopropyl-substituted anthraquinones via Friedel–Crafts acylations: migration of isopropyl groups
Authors: Chakiri Abdel B. , Hodge Philip
Published: August 2017

Friedel–Crafts reactions of isopropyl-substituted benzenes with phthalic anhydride in the presence of aluminium trichloride, followed by cyclization of the products with strong sulfuric acid give, as expected, anthraquinones. The syntheses, however, often afford more than one anthraquinone. In some cases the isopropyl groups migrate cleanly to other ring positions; in other cases they are lost.
The morphology of the inner ear of squamate reptiles and its bearing on the origin of snakes
Authors: Palci Alessandro , Hutchinson Mark N. , Caldwell Michael W. , Lee Michael S. Y.
Published: August 2017

The inner ear morphology of 80 snake and lizard species, representative of a range of ecologies, is here analysed and compared to that of the fossil stem snake
Dinilysia patagonica
, using three-dimensional geometric morphometrics. Inner ear morphology is linked to phylogeny (we find here a strong phylogenetic signal in the data that can complicate ecological correlations), but also correlated with ecology, with
Dinilysia
resembling certain semi-fossorial forms (
Xenopeltis
and
Cylindrophis
), consistent with previous reports. We here also find striking resemblances between
Dinilysia
and some semi-aquatic snakes, such as
Myron
(Caenophidia, Homalopsidae). Therefore, the inner ear morphology of
Dinilysia
is consistent with semi-aquatic as well as semi-fossorial habits: the most similar forms are either semi-fossorial burrowers with a strong affinity to water (
Xenopeltis
and
Cylindrophis
) or amphibious, intertidal forms which shelter in burrows (
Myron).
Notably,
Dinilysia
does not cluster as closely with snakes with exclusively terrestrial or obligate burrowing habits (e.g. scolecophidians and uropeltids). Moreover, despite the above similarities,
Dinilysia
also occupies a totally unique morphospace, raising issues with linking it with any particular ecological category.
Perception of the average size of multiple objects in chimpanzees (
Pan troglodytes
)
Authors: Imura Tomoko , Kawakami Fumito , Shirai Nobu , Tomonaga Masaki
Published: August 2017

Humans can extract statistical information, such as the average size of a group of objects or the general emotion of faces in a crowd without paying attention to any individual object or face. To determine whether summary perception is unique to humans, we investigated the evolutional origins of this ability by assessing whether chimpanzees, which are closely related to humans, can also determine the average size of multiple visual objects. Five chimpanzees and 18 humans were able to choose the array in which the average size was larger, when presented with a pair of arrays, each containing 12 circles of different or the same sizes. Furthermore, both species were more accurate in judging the average size of arrays consisting of 12 circles of different or the same sizes than they were in judging the average size of arrays consisting of a single circle. Our findings could not be explained by the use of a strategy in which the chimpanzee detected the largest or smallest circle among those in the array. Our study provides the first evidence that chimpanzees can perceive the average size of multiple visual objects. This indicates that the ability to compute the statistical properties of a complex visual scene is not unique to humans, but is shared between both species.
A hypothesis on a role of oxytocin in the social mechanisms of speech and vocal learning
Authors: Theofanopoulou Constantina , Boeckx Cedric , Jarvis Erich D.
Published: August 2017

Language acquisition in humans and song learning in songbirds naturally happen as a social learning experience, providing an excellent opportunity to reveal social motivation and reward mechanisms that boost sensorimotor learning. Our knowledge about the molecules and circuits that control these social mechanisms for vocal learning and language is limited. Here we propose a hypothesis of a role for oxytocin (OT) in the social motivation and evolution of vocal learning and language. Building upon existing evidence, we suggest specific neural pathways and mechanisms through which OT might modulate vocal learning circuits in specific developmental stages.
Mechanics of evolutionary digit reduction in fossil horses (Equidae)
Authors: McHorse Brianna K. , Biewener Andrew A. , Pierce Stephanie E.
Published: August 2017

Digit reduction is a major trend that characterizes horse evolution, but its causes and consequences have rarely been quantitatively tested. Using beam analysis on fossilized centre metapodials, we tested how locomotor bone stresses changed with digit reduction and increasing body size across the horse lineage. Internal bone geometry was captured from 13 fossil horse genera that covered the breadth of the equid phylogeny and the spectrum of digit reduction and body sizes, from
Hyracotherium
to
Equus
. To account for the load-bearing role of side digits, a novel, continuous measure of digit reduction was also established—toe reduction index (TRI). Our results show that without accounting for side digits, three-toed horses as late as
Parahippus
would have experienced physiologically untenable bone stresses. Conversely, when side digits are modelled as load-bearing, species at the base of the horse radiation through
Equus
probably maintained a similar safety factor to fracture stress. We conclude that the centre metapodial compensated for evolutionary digit reduction and body mass increases by becoming more resistant to bending through substantial positive allometry in internal geometry. These results lend support to two historical hypotheses: that increasing body mass selected for a single, robust metapodial rather than several smaller ones; and that, as horse limbs became elongated, the cost of inertia from the side toes outweighed their utility for stabilization or load-bearing.
Bayesian Efficient Coding
Authors: Park Il Memming , Pillow Jonathan W.
Published: August 2017

The efficient coding hypothesis, which proposes that neurons are optimized to maximize information about the environment, has provided a guiding theoretical framework for sensory and systems neuroscience. More recently, a theory known as the Bayesian Brain hypothesis has focused on the brain's ability to integrate sensory and prior sources of information in order to perform Bayesian inference. However, there is as yet no comprehensive theory connecting these two theoretical frameworks. Here we bridge this gap by formalizing a Bayesian theory of efficient coding. We define Bayesian efficient codes in terms of four basic ingredients: (1) a stimulus prior distribution; (2) an encoding model; (3) a capacity constraint, specifying a neural resource limit; and (4) a loss function, quantifying the desirability or undesirability of various posterior distributions. Classic efficient codes can be seen as a special case in which the loss function is the posterior entropy, leading to a code that maximizes mutual information, but alternate loss functions give solutions that differ dramatically from information-maximizing codes. In particular, we show that decorrelation of sensory inputs, which is optimal under classic efficient codes in low-noise settings, can be disadvantageous for loss functions that penalize large errors. Bayesian efficient coding therefore enlarges the family of normatively optimal codes and provides a more general framework for understanding the design principles of sensory systems. We examine Bayesian efficient codes for linear receptive fields and nonlinear input-output functions, and show that our theory invites reinterpretation of Laughlin's seminal analysis of efficient coding in the blowfly visual system.
Tim-3 co-stimulation promotes short-term effector T cells, restricts memory precursors and is dispensable for T cell exhaustion
Authors: Avery Lyndsay , Szymczak-Workman Andrea L. , Kane Lawrence P.
Published: August 2017

Tim-3 is highly expressed on a subset of T cells during T cell exhaustion, in settings of chronic viral infection and tumors (1, 2). Using LCMV Clone-13, a model for chronic infection, we have found that Tim-3 is neither necessary nor sufficient for the development of T cell exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance to PD-L1 blockade therapy during chronic infection. Strikingly, expression of Tim-3 promoted development of short-term effector T cells, at the expense of memory precursor development, after acute LCMV infection. These effects were accompanied by increased Akt/mTOR signaling in T cells expressing endogenous or ectopic Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells from Tim-3 deficient mice. Thus, Tim-3 is essential for optimal effector T cell responses, but may also contribute to exhaustion, by restricting development of long-lived memory T cells, including PD-1int“stem-like” exhausted T cells that expand during PD-1 pathway blockade. Taken together, our results suggest that Tim-3 is actually more similar to co-stimulatory receptors that are upregulated after T cell activation, rather than a dominant inhibitory protein like PD-1. These findings have significant implications for the development of anti-Tim-3 antibodies as therapeutic agents.

Significance

During a chronic viral infection, prolonged exposure to viral antigens leads to dysfunction or “exhaustion” of T cells specific to the virus, a condition also observed in T cells that infiltrate tumors. The exhausted state is associated with expression of specific cell-surface proteins, some of which may inhibit T cell activation. Expression of Tim-3 is associated with acquisition of T cell exhaustion, although it is also expressed transiently during acute infection. Here we provide evidence that a major function of Tim-3 is to enhance T cell activation, during either acute or chronic viral infection. However, Tim-3 is not required for development of exhaustion. Thus, we propose that Tim-3 would be better described as a stimulatory, rather than inhibitory, protein.
Index hopping on the Illumina HiseqX platform and its consequences for ancient DNA studies
Authors: Valk Tom van der , Vezzi Francesco , Ormestad Mattias , Dalén Love , Guschanski Katerina
Published: August 2017

The high-throughput capacities of the Illumina sequencing platforms and the possibility to label samples individually have encouraged a wide use of sample multiplexing. However, this practice results in read misassignment (usually <1%) across samples sequenced on the same lane. Alarmingly high rates of read misassignment of up to 10% were reported for the latest generation of lllumina sequencing machines. This may make future use of the newest generation of platforms prohibitive, particularly in studies that rely on low quantity and quality samples, such as historical and archaeological specimens. Here, we rely on barcodes, short sequences that are ligated to both ends of the DNA insert, to directly quantify the rate of index hopping in 100-year old museum-preserved gorilla (Gorilla beringei) samples. Correcting for multiple sources of noise, we identify on average 0.470% of reads containing a hopped index. We show that sample-specific quantity of misassigned reads depend on the number of reads that any given sample contributes to the total sequencing pool, so that samples with few sequenced reads receive the greatest proportion of misassigned reads. Ancient DNA samples are particularly affected, since they often differ widely in endogenous content. Through extensive simulations we show that even low index-hopping rates lead to biases in ancient DNA studies when multiplexing samples with different quantities of input material.
Generation and validation of afloxed FosBmouse line
Authors: Ohnishi Yoshinori N. , Eagle Andrew L. , Ohnishi Yoko H. , Cahill Michael E. , Wirtz Alexis J. , Robison Alfred J. , Nestler Eric J.
Published: August 2017

Expression of theFosBgene has been studied extensively in many fields using a variety of tools. However, previous techniques have had a variety of caveats, from potential off-target effects (e.g., overexpression of FosB, ΔFosB, or a dominant negative mutant of JunD, termed ΔJunD) or confounding developmental effects (e.g., the constitutiveFosBknockout mouse). Therefore, we sought to create afloxed FosBmouse line that will allow true silencing of theFosBgene with both spatial and temporal control. Here, we detail the cloning strategy, production, and validation of thefloxed FosBmouse. We demonstrate methodology for breeding and genotyping, and show that viral-mediated expression of Cre recombinase in a targeted, discrete brain region ablates expression of theFosBgene infloxedbut not wild type mice. Thus, thefloxed FosBmouse presented here represents an important new tool for the continued investigation of this critical gene.
PDB-NMA of a Protein Homodimer Reproduces Distinct Experimental Motility Asymmetry
Authors: Tirion Monique M. , ben-Avraham Daniel
Published: August 2017

We have extended our analytically derived PDB-NMA formulation, ATMAN [1], to include protein dimers using mixed internal and Cartesian coordinates. A test case on a 1.3Å resolution model of a small homodimer, ActVA-ORF6, consisting of two 112-residue subunits identically folded in a compact 50Å sphere, reproduces the distinct experimental Debye-Waller motility asymmetry for the two chains, demonstrating that structure sensitively selects vibrational signatures. The vibrational analysis of this PDB entry, together with biochemical and crystallographic data, demonstrates the cooperative nature of the dimeric interaction of the two subunits and suggests a mechanical model for subunit interconversion during the catalytic cycle.
Global transcriptome analysis ofAedes aegyptimosquitoes in response to Zika virus infection
Authors: Etebari Kayvan , Hegde Shivanand , Saldaña Miguel A , Widen Steven G , Wood Thomas G , Asgari Sassan , Hughes Grant L
Published: August 2017

Zika virus (ZIKV) of theFlaviviridaefamily is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquitoAedes aegyptithat also vectors dengue virus, however little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of wholeAe. aegyptimosquitoes in response to ZIKV infection at 2, 7, and 14 days post-infection using RNA-Seq. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic process, cellular process and proteolysis. In addition, 486 long intergenic non-coding RNAs were identified that were altered upon ZIKV infection. Further, we found correlational changes of a number of potential mRNA target genes with that of altered host microRNAs. The outcomes provide a basic understanding ofAe. aegyptiresponses to ZIKV and helps to determine host factors involved in replication or mosquito host anti-viral response against the virus.

Importance

Vector-borne viruses pose great risks on human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response ofAedes aegyptimosquitoes to Zika virus infection. Results showed large changes both in coding and long non-coding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.
SeroBA: rapid high-throughput serotyping ofStreptococcus pneumoniaefrom whole genome sequence data
Authors: Epping Lennard , van Tonder Andries J. , Gladstone Rebecca A. ,   The Global Pneumococcal Sequencing Consortium, Bentley Stephen D. , Page Andrew J. , Keane Jacqueline A.
Published: August 2017

Streptococcus pneumoniaeis responsible for 240,000 - 460,000 deaths in children under 5 years of age each year. Accurate identification of pneumococcal serotypes is important for tracking the distribution and evolution of serotypes following the introduction of effective vaccines. Recent efforts have been made to infer serotypes directly from genomic data but current software approaches are limited and do not scale well. Here, we introduce a novel method, SeroBA, which uses a hybrid assembly and mapping approach. We compared SeroBA against real and simulated data and present results on the concordance and computational performance against a validation dataset, the robustness and scalability when analysing a large dataset, and the impact of varying the depth of coverage in thecpslocus region on sequence-based serotyping. SeroBA can predict serotypes, by identifying thecpslocus, directly from raw whole genome sequencing read data with 98% concordance using ak-mer based method, can process 10,000 samples in just over 1 day using a standard server and can call serotypes at a coverage as low as 10x. SeroBA is implemented in Python3 and is freely available under an open source GPLv3 license from:https://github.com/sanger-pathogens/seroba.

DATA SUMMARY

The reference genomeStreptococcus pneumoniaeATCC 700669 is available from National Center for Biotechnology Information (NCBI) with the accession number: FM211187

Simulated paired end reads for experiment 2 have been deposited in FigShare:https://doi.org/10.6084/m9.figshare.5086054.v1

Accession numbers for all other experiments are listed in Supplementary Table S1 and Supplementary Table S2.

I/We confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. ⊠

IMPACT STATEMENT

This article describes SeroBA, a A-mer based method for predicting the serotypes ofStreptococcus pneumoniaefrom Whole Genome Sequencing (WGS) data. SeroBA can identify 92 serotypes and 2 subtypes with constant memory usage and low computational costs. We showed that SeroBA is able to reliably predict serotypes at a depth of coverage as low as 10x and is scalable to large datasets.
The neural encoding of information prediction errors during non-instrumental information seeking
Authors: Brydevall Maja , Bennett Daniel , Murawski Carsten , Bode Stefan
Published: August 2017

In a dynamic world, accurate beliefs about the environment are vital for survival, and individuals should therefore regularly seek out new information with which to update their beliefs. This aspect of behaviour is not well captured by standard theories of decision making, and the neural mechanisms of information seeking remain unclear. One recent theory posits that valuation of information results from representation of informative stimuli within canonical neural reward-processing circuits, even if that information lacks instrumental use. We investigated this question by recording EEG from twenty-three human participants performing a non-instrumental information-seeking task. In this task, participants could pay a monetary cost to receive advance information about the likelihood of receiving reward in a lottery at the end of each trial. Behavioural results showed that participants were willing to incur considerable monetary costs to acquire early but non-instrumental information. Analysis of the event-related potential elicited by informative cues revealed that the feedback-related negativity independently encoded both an information prediction error and a reward prediction error. These findings are consistent with the hypothesis that information seeking results from processing of information within neural reward circuits, and suggests that information may represent a distinct dimension of valuation in decision making under uncertainty.
Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation
Authors: Li Lucia M. , Violante Ines R. , Leech Rob , Ross Ewan , Hampshire Adam , Opitz Alexander , Rothwell John C. , Carmichael David W. , Sharp David J.
Published: August 2017

Transcranial direct current stimulation (TDCS) has been widely used to improve cognitive function. However, current deficiencies in mechanistic understanding hinders wider applicability. To clarify its physiological effects, we acquired fMRI whilst simultaneously acquiring TDCS to the right inferior frontal gyrus (rIFG) of healthy human participants, a region involved in coordinating activity within brain networks. TDCS caused widespread modulation of network activity depending on brain state (‘rest’ or choice reaction time task) and polarity (anodal or cathodal). During task, TDCS increased salience network activation and default mode network deactivation, but had the opposite effect during ‘rest’. Furthermore, there was an interaction between brain state and TDCS polarity, with cathodal effects more pronounced during task performance and anodal effects more pronounced during ‘rest’. Overall, we show that rIFG TDCS produces brain state and polarity dependent effects within large-scale cognitive networks, in a manner that goes beyond predictions from the current literature.
Role for Ribosome-Associated Complex and Stress-Seventy subfamily B (RAC-Ssb) in integral membrane protein translation
Authors: Acosta-Sampson Ligia , Döring Kristina , Lin Yuping , Yu Vivian Y. , Bukau Bernd , Kramer Günter , Cate Jamie H. D.
Published: August 2017

Targeting of most integral membrane proteins to the endoplasmic reticulum is controlled by the signal recognition particle (SRP), which recognizes a hydrophobic signal sequence near the protein N-terminus. Proper folding of these proteins is monitored by the unfolded protein response, and involves protein degradation pathways to ensure quality control. Here, we identify a new pathway for quality control of major facilitator superfamily transporters that occurs before the first transmembrane helix–the signal sequence recognized by SRP–is made by the ribosome. Increased rates of translation elongation of the N-terminal sequence of these integral membrane proteins can divert the nascent protein chains to the ribosome-associated complex (RAC) and Stress-Seventy Subfamily B (Ssb) chaperones. We also show that quality control of integral membrane proteins by RAC-Ssb couples translation rate to the unfolded protein response, which has implications for understanding mechanisms underlying human disease and protein production in biotechnology.
Identification of Iridoid Synthases fromNepetaspecies: Iridoid cyclization does not determine nepetalactone stereochemistry
Authors: Sherden Nathaniel H. , Lichman Benjamin , Caputi Lorenzo , Zhao Dongyan , Kamileen Mohamed O. , Robin Buell C. , O’Connor Sarah E.
Published: August 2017

Graphical Abstract

Iridoid synthase fromNepeta cateria(catnip) andNepeta mussinii, have been cloned and characterized.

Nepetalactones are iridoid monoterpenes with a broad range of biological activities produced by plants in theNepetagenus. However, none of the genes for nepetalactone biosynthesis have been discovered. Here we report the transcriptomes of twoNepetaspecies, each with distinctive profiles of nepetalactone stereoisomers. As a starting point for investigation of nepetalactone biosynthesis inNepeta, these transcriptomes were used to identify candidate genes for iridoid synthase homologs, an enzyme that has been shown to form the core iridoid skeleton in several iridoid producing plant species. Iridoid synthase homologs identified from the transcriptomes were cloned, heterologously expressed, and then assayed with the 8-oxogeranial substrate. These experiments revealed that catalytically active iridoid synthase enzymes are present inNepeta,though there are unusual mutations in key active site residues. Nevertheless, these enzymes exhibit similar catalytic activity and product profile compared to previously reported iridoid synthases from other plants. Notably, four nepetalactone stereoisomers with differing stereochemistry at the 4αand 7αpositions – which are generated during the iridoid synthase reaction – are observed at different ratios in variousNepetaspecies. This work strongly suggests that the variable stereochemistry at these 4αand 7αpositions of nepetalactone diastereomers is established further downstream in the iridoid pathway inNepeta. Overall, this work provides a gateway into the biosynthesis of nepetalactones inNepeta.

Highlights

Species within theNepetagenus (such as catnip) produce nepetalactone iridoids

The enzymes that produce the iridoid scaffold of nepetalactone were identified from two species ofNepeta

The iridoid synthase enzymes are not responsible for the stereochemical variation in these iridoids
Helpers increase daily survival rate of Southern Lapwing (Vanellus chilensis) nests during the incubation stage
Authors: Santos Eduardo S. A. , Macedo Regina H.
Published: August 2017

Cooperative breeding is characterized by reproduction in the presence of helpers. What impact these helpers have on the reproductive success of group members is one of the long-standing questions in the cooperative breeding literature. In cooperative species, helpers are known to provide benefits during multiple stages or at a particular stage of the reproductive cycle. The aim of this study was to investigate whether helpers increased the daily survival rate of nests during the incubation stage in the Southern Lapwing (Vanellus chilensis), a crested plover with a cooperative breeding system. Southern Lapwings have a variable mating system, with some breeding groups composed of unassisted pairs, and others that breed in the presence of helpers. Our best supported model indicated a positive effect of the presence of helpers on the daily survival rate of nests, leading to a probability of nest success (i.e., survival until hatching) of 83%, compared to 51% for nests of unassisted pairs. But a null model had a similar model weight as the best supported model and was the second-best model. Our study provides evidence that helpers influence egg survival during the egg-incubation stage, which could influence the fitness of breeders.
Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice
Authors: Hirose Misa , Schilf Paul , Gupta Yask , Zarse Kim , Künstner Axel , Busch Hauke , Yin Junping , Wright Marvin N , Ziegler Andreas , Vallier Marie , Belheouane Meriem , Baines John F , Tautz Diethard , Johann Kornelia , Oelkrug Rebecca , Mittag Jens , Lehnert Hendrik , Othman Alaa , Jöhren Olaf , Schwaninger Markus , Prehn Cornelia , Adamski Jerzy , Shima Kensuke , Rupp Jan , Haesler Robert , Fuellen Georg , Köhling Rüdiger , Ristow Michael , Ibrahim Saleh M
Published: August 2017

Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e. the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum of diseases but also physiological processes, including endurance exercise performance in athletes. However, the phenotypic consequences of limited levels of naturally-arising heteroplasmy have not been experimentally studied to date. We hence generated a conplastic mouse strain carrying the mitochondrial genome of a AKR/J mouse strain (B6-mtAKR) together with a C57BL/6J nuclear genomic background, leading to >20% heteroplasmy in the origin of light-strand DNA replication (OriL). These conplastic mice demonstrate a shorter lifespan as well as dysregulation of multiple metabolic pathways, culminating in impaired glucose metabolism, compared to wild-type C57BL/6J mice carrying lower levels of heteroplasmy. Our results indicate that physiologically relevant differences in mtDNA heteroplasmy levels at a single, functionally important site impair metabolic health and lifespan in mice.

Highlights

We identify heteroplasmy of the adenine-repeat variation (9 to 13A) in nt5172 in the origin of light-strand DNA replication (OriL) in inbred mice.

B6-mtAKRmice carry >20% 12A heteroplasmy in the OriL, while B6 mice carry only ∼ 10% heteroplasmy.

The level of 12A heteroplasmy correlates to mtDNA copy number, glucose metabolism, and lifespan in mice.

Given the established role of mtDNA heteroplasmy in regards to endurance exercise performance in athletes, these findings may impact our understanding of metabolism and aging in humans.
Tadpole-like conformations of huntingtin exon 1 with expanded polyglutamine engenders novel interactions in cells
Authors: Newcombe Estella A. , Ruff Kiersten M. , Sethi Ashish , Ormsby Angelique R. , Ramdzan Yasmin M. , Fox Archa , Purcell Anthony W. , Gooley Paul R. , Pappu Rohit V. , Hatters Danny M.
Published: August 2017

Soluble huntingtin exon 1 (Httex1) with expanded polyglutamine (polyQ) engenders neurotoxicity in Huntington’s disease. To uncover the physical basis of this toxicity, we performed structural studies of soluble Httex1 for wild type and mutant polyQ lengths. Nuclear magnetic resonance experiments show evidence for conformational rigidity across the polyQ region. In contrast, hydrogen-deuterium exchange shows absence of backbone amide protection, suggesting negligible persistence of hydrogen bonds. The seemingly conflicting results are explained by all-atom simulations, which show that Httex1 adoptstadpole-likestructures with a globular head encompassing the N-terminal amphipathic and polyQ regions and the tail encompassing the C-terminal proline-rich region. The surface area of the globular domain increases monotonically with polyQ length. This stimulates sharp increases in gain-of-function interactions in cells for expanded polyQ, and one of these interactions is with the stress-granule protein Fus. Our results highlight plausible connections between Httex1 structure and routes to neurotoxicity.
Active ribosome profiling with RiboLace
Authors: Clamer Massimiliano , Tebaldi Toma , Lauria Fabio , Bernabò Paola , Gómez-Biagi Rodolfo F. , Perenthaler Elena , Gubert Daniele , Pasquardini Laura , Guella Graziano , Groen Ewout J.N. , Gillingwater Thomas H. , Quattrone Alessandro , Viero Gabriella
Published: August 2017

Ribosome profiling, or Ribo-Seq, is based around large-scale sequencing of RNA fragments protected from nuclease digestion by ribosomes. Thanks to its unique ability to provide positional information concerning ribosomes flowing along transcripts, this method can be used to shed light on mechanistic aspects of translation. However, current Ribo-Seq approaches lack the ability to distinguish between fragments protected by ribosomes in active translation or by inactive ribosomes. To overcome these significant limitation, we developed RiboLace: a novel method based on an original puromycin-containing molecule capable of isolating active ribosomes by means of an antibody-free and tag-free pull-down approach. RiboLace is fast, works reliably with low amounts of input material, and can be easily and rapidly applied bothin vitroandin vivo, thereby generating a global snapshot of active ribosome footprints at single nucleotide resolution.
Lead-lag relationship between futures and spot FX market in India
Authors: Kharbanda Varuna , Singh Archana
Published: August 2017

Purpose

The purpose of this paper is to study the lead-lag relationship between the futures and spot foreign exchange (FX) market in India to understand the price discovery mechanism and the relationship between these two markets.

Design/methodology/approach

The estimation of lead-lag relationship is realized in three steps. First unit root and stationarity tests (Augmented Dickey-Fuller, Phillips-Perron, and Kwiatkowski-Phillips-Schmidt-Shin) are applied to check the stationarity of the data. Second, cointegration tests (Engle and Granger’s residual based approach and Johansen’s cointegration test) are applied to determine long run relationship between the markets. Third, error correction estimation is carried out by applying Vector Error Correction Model (VECM) to determine the leading market.

Findings

The study finds that there is a long run relationship between the futures and spot market where the futures market has emerged as the leading market for the four currencies studied in the paper.

Originality/value

Majorly, the studies on Indian FX market limit themselves to identifying the efficiency of the market and the studies which talk about the lead-lag relationship focus on the Indian stock market. This paper enhances the existing literature on Indian FX market by exploring the less explored subject of the lead-lag relationship between futures and spot FX market in India.
The interrelationship between net interest margin and non-interest income: evidence from Vietnam
Authors: Le Tu DQ
Published: August 2017

Purpose

The purpose of this paper is to investigate the interrelationship between non-interest income (NII) and net interest margin (NIM) in the Vietnamese banking system between 2006 and 2015. Thereafter, the impact of NII on risk-adjusted returns is also examined.

Design/methodology/approach

Various analysis techniques are used to achieve the research objectives.

Findings

The findings show a negative two-way link between NII and NIM, thus supporting the subsidisation hypothesis. Furthermore, NII is found to have a negative impact on risk-adjusted returns. When observing this relationship in sub-samples, the findings indicate that the negative impact of NII on risk-adjusted returns still holds in the first subsample (2006-2011). The coefficient of NII becomes positive but not significant for the subsequent period (2012-2015). In addition, the Spearman rank-order correlations of returns on assets and NII for both sub-samples are negative. Together, the author concludes that there are no diversification benefits in the Vietnamese banking system.

Practical implications

The evidence suggests a trade-off between non-interest activities and traditional lending ones. In addition, the findings demonstrate that the Vietnamese banks may use NIIs to expand leverage and herd by coordinating NII strategy during the economic downturns. Thus, the banking system may be exposed to a greater risk. The research has implications for bank supervisors, policy-makers and bank managers.

Originality/value

This study is the first attempt to investigate the interrelationships between net NII and NIM in the Vietnamese banking system.