bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen-sensing neurons reciprocally regulate peripheral lipid metabolism via neuropeptide signaling inCaenorhabditis elegans
Authors: Hussey Rosalind , Witham Emily , Vanstrum Erik , Mesgarzadeh Jaleh , Ratanpal Harkaranveer , Srinivasan Supriya
Published: May 2017

The mechanisms by which the sensory environment instructs metabolic homeostasis remains poorly understood. In this report, we show that oxygen, a potent environmental signal, is an important regulator of whole body lipid metabolism.C. elegansoxygen-sensing neurons reciprocally regulate peripheral lipid metabolism under normoxia in the following way: under high oxygen and food absence, URX sensory neurons are activated, and stimulate fat loss in the intestine, the major metabolic organ forC. elegans. Under lower oxygen conditions or when food is present, the BAG sensory neurons respond by repressing the resting properties of the URX neurons. A genetic screen to identify modulators of this effect led to the identification of a BAG-neuron-specific neuropeptide called FLP-17, whose cognate receptor EGL-6 functions in URX neurons. Thus, BAG sensory neurons counterbalance the metabolic effect of tonically active URX neurons via neuropeptide communication. The combined regulatory actions of these neurons serve to precisely tune the rate and extent of fat loss, to the availability of food and oxygen.
Continuity and admixture in the last five millennia of Levantine history from ancient Canaanite and present-day Lebanese genome sequences
Authors: Haber Marc , Doumet-Serhal Claude , Scheib Christiana , Xue Yali , Danecek Petr , Mezzavilla Massimo , Youhanna Sonia , Martiniano Rui , Prado-Martinez Javier , Szpak Michal , Matisoo-Smith Elizabeth , Schutkowski Holger , Mikulski Richard , Zalloua Pierre , Kivisild Toomas , Tyler-Smith Chris
Published: May 2017

The Canaanites inhabited the Levant region during the Bronze Age and established a culture which became influential in the Near East and beyond. However, the Canaanites, unlike most other ancient Near Easterners of this period, left few surviving textual records and thus their origin and relationship to ancient and present-day populations remain unclear. In this study, we sequenced five whole-genomes from ~3,700-year-old individuals from the city of Sidon, a major Canaanite city-state on the Eastern Mediterranean coast. We also sequenced the genomes of 99 individuals from present-day Lebanon to catalogue modern Levantine genetic diversity. We find that a Bronze Age Canaanite-related ancestry was widespread in the region, shared among urban populations inhabiting the coast (Sidon) and inland populations (Jordan) who likely lived in farming societies or were pastoral nomads. This Canaanite-related ancestry derived from mixture between local Neolithic populations and eastern migrants genetically related to Chalcolithic Iranians. We estimate, using linkage-disequilibrium decay patterns, that admixture occurred 6,600-3,550 years ago, coinciding with massive population movements in the mid-Holocene triggered by aridification ~4,200 years ago. We show that present-day Lebanese derive most of their ancestry from a Canaanite-related population, which therefore implies substantial genetic continuity in the Levant since at least the Bronze Age. In addition, we find Eurasian ancestry in the Lebanese not present in Bronze Age or earlier Levantines. We estimate this Eurasian ancestry arrived in the Levant around 3,750-2,170 years ago during a period of successive conquests by distant populations such as the Persians and Macedonians.
Evolution of bird communication signals: transference between signals mediated by sensory drive
Authors: Laverde-R. Oscar , Ryan Michael J. , Cadena Carlos Daniel
Published: May 2017

Animals communicate using signals perceived via multiple sensory modalities but usually invest more heavily in one of type of signal. This pattern, observed by Darwin1and many researchers since, led to development of the transfer hypothesis (see also transferal effect2and tradeoff hypothesis3,4), which predicts a negative relationship between investment in different signaling modalities dictated by the relative costs and benefits of each. One factor that influences costs and benefits, and is central to the sensory drive hypothesis5posed to account for signal evolution, is the suitability of the environment for different types of signals. Movement into a dark habitat, for example, should favor investment in acoustic over visual signals. We use phylogenetic comparative methods to analyze the joint effect of transfer and sensory drive on plumage and song variation in 52 species of a large radiation of passerine birds, the New World warblers (Parulidae), and to estimate temporal patterns in the accumulation of differences in visual and vocal signals and habitat along the evolutionary history of this lineage. We found evidence for the predicted negative correlations between a variety of song and plumage traits that vary with habitat type. Plumage contrast to background and chromatic diversity were both negatively related to syllable variety when vegetation structure was a covariate: birds with a greater variety of song syllables and less colorful plumages live in closed or darker habitats. Also as predicted, achromatic or brightness diversity was related to vegetation structure. In addition, disparity-through-time analyses showed that when one set of traits (i.e. songs or colors) diversified at a relatively high rate the other did not, as predicted by the transfer hypothesis. Our results show that sensory drive influences the transfer of investment between traits in different sensory modalities. This interaction between mechanisms shaping signals may be a major determinant in the evolution of animal communication.
Transcription of Repeats Activates INterferon (TRAIN) in response to chromatin destabilization induced with anti-cancer small molecule
Authors: Leonova Katerina , Safina Alfiya , Nesher Elimelech , Sandlesh Poorva , Pratt Rachel , Burkhart Catherine , Lipchick Britney , Frangou Costakis , Koman Igor , Wang Jianmin , Kirsanov Kirill , Yakubovskaya Marianna G. , Gudkov Andrei V. , Gurova Katerina
Published: May 2017

The anticancer activity of genotoxic agents has been intensively studied, while the mechanisms of action of drugs destabilizing the epigenome are far less understood. We previously found that DNA hypomethylation in the absence of p53 leads to transcriptional desilencing of repetitive DNA elements, such as pericentromeric repeats and endogenous retroelements, which is associated with an interferon type I response, a phenomenon we named TRAIN (Transcription ofRepeatsActivatesINterferon). Here, we report that curaxin, a small molecule anticancer drug candidate, which destabilizes nucleosomes via disruption of histone/DNA interactions, can induce TRAIN independently of the p53 status of a cell. Furthermore, curaxin inhibits oncogene-induced transformation in an interferon-dependent manner, suggesting that cancer prevention by curaxin, previously attributed to its p53-activating and NF-kappaB-inhibiting activities, may also involve the induction of the interferon response to epigenetic derepression of the cellular “repeatome.” Moreover, we observed that another type of drugs decondensing chromatin, histone deacetylase inhibitor, also induces TRAIN. Thus, we proposed that TRAIN may be one of the mechanisms ensuring epigenetic integrity of cells via elimination of cells with desilenced chromatin.
A Possible Role Of Microglia In Zika Virus Infection Of The Fetal Human Brain
Authors: Muffat Julien , Li Yun , Omer Attya , Durbin Ann , Bosch Irene , Bakiasi Grisilda , Richards Edward , Meyer Aaron , Gehrke Lee , Jaenisch Rudolf
Published: May 2017

Maternal Zika virus (ZIKV) infection during pregnancy is increasingly recognized as the cause of an epidemic of microcephaly and other neurological anomalies in human fetuses. However, it remains unclear how ZIKV gains access to the highly vulnerable population of neural progenitors of the fetal central nervous system (CNS), and which cell types of the CNS may serve as viral reservoirs. To model viral interaction with cells of the fetal CNS invitro, we investigated the tropism of ZIKV for different iPS-derived human cells, with a particular focus on microglia-like cells derived from human pluripotent stem cells. We show that ZIKV infected isogenic neural progenitors, astrocytes and microglia-like cells, but was only cytotoxic to neural progenitors. Infected glial cells propagated the virus and maintained viral load over time, leading to viral spread to susceptible cells. ZIKV-infected microglia, when co-cultured with pre-established neural spheroids, invaded the tissue and initiated neural infection. Since microglia derive from primitive macrophages originating in anatomical proximity to the maternal vasculature of the placenta, we propose that they may act invivoas a viral reservoir for ZIKV and, owing to their natural ability to traverse the embryo, can establish infection of the fetal brain. Infection of immature neural stem cells by invading microglia may occur in the early stages of pregnancy, before vascular circulation is established. Our data are also consistent with the virus affecting the integrity of the blood-brain barrier (BBB), which may allow infection of the brain at later stages.
Modality-independent coding of scene categories in prefrontal cortex
Authors: Jung Yaelan , Larsen Bart , Walther Dirk B.
Published: May 2017

Natural environments convey information through multiple sensory modalities, all of which contribute to people’s percepts. Although it has been shown that visual or auditory content of scene categories can be decoded from brain activity, it remains unclear where and how humans integrate different sensory inputs and represent scene information beyond a specific sensory modality domain. To address this question, we investigated how categories of scene images and sounds are represented in several brain regions. A mixed gender group of healthy human subjects participated the present study, where their brain activity was measured with fMRI while viewing images or listening to sounds of different places. We found that both visual and auditory scene categories can be decoded not only from modality-specific areas, but also from several brain regions in the temporal, parietal, and prefrontal cortex. Intriguingly, only in the prefrontal cortex, but not in any other regions, categories of scene images and sounds appear to be represented in similar activation patterns, suggesting that scene representations in the prefrontal cortex are modality-independent. Furthermore, the error patterns of neural decoders indicate that category-specific neural activity patterns in the middle and superior frontal gyri are tightly linked to categorization behavior. Our findings demonstrate that complex scene information is represented at an abstract level in the prefrontal cortex, regardless of the sensory modality of the stimulus.

Statement of Significance

Our experience in daily life requires the integration of multiple sensory inputs such as images, sounds, or scents from the environment. Here, for the first time, we investigated where and how in the brain information about the natural environment from multiple senses is merged to form modality-independent representations of scene categories. We show direct decoding of scene categories across sensory modalities from patterns of neural activity in the prefrontal cortex. We also conclusively tie these neural representations to human categorization behavior based on the errors from the neural decoder and behavior. Our findings suggest that the prefrontal cortex is a central hub for integrating sensory information and computing modality-independent representations of scene categories.
Exploiting theZIP4homologue within the wheatPh1locus has identified two lines exhibiting homoeologous crossover in wheat-wild relative hybrids
Authors: Rey María-Dolores , Martín Azahara C , Higgins Janet , Swarbreck David , Uauy Cristobal , Shaw Peter , Moore Graham
Published: May 2017

Despite possessing related ancestral genomes, hexaploid wheat behaves as a diploid during meiosis. The wheatPh1locus promotes accurate synapsis and crossover of homologous chromosomes. Interspecific hybrids between wheat and wild relatives are exploited by breeders to introgress important traits from wild relatives into wheat, although in hybrids between hexaploid wheat and wild relatives, which possess only homoeologues, crossovers do not take place during meiosis at metaphase I. However, in hybrids betweenPh1deletion mutants and wild relatives, crossovers do take place. A singlePh1deletion (ph1b) mutant has been exploited for the last 40 years for this activity. We show here that selection of chemical induced mutant lines possessing mutations inTaZIP4-B2exhibit high levels of homoeologous crossovers when crossed with a wild relative. Exploitation ofTazip4-B2mutants rather than mutants with wholePh1locus deletions may improve introgression of wild relative chromosome segments into wheat. Such mutant lines may be more stable over multiple generations, as multivalents causing accumulation of chromosome translocations are less frequent.

Key message

Exploiting theZIP4homologue within the wheatPh1locus has identified two wheat mutants through a non-GM route, which can be exploited as an alternative to the Chinese Springph1bmutant in wheat introgression strategies.
Specific Virus-Host Genome Interactions Revealed by Tethered Chromosome Conformation Capture
Authors: Li Haochen , Kalhor Reza , Li Bing , Su Trent , Berk Arnold J. , Kurdistani Siavash K. , Alber Frank , Chen Lin
Published: May 2017

Viruses have evolved a variety of mechanisms to interact with host cells for their adaptive benefits, including subverting host immune responses and hijacking host DNA replication/transcription machineries [1–3]. Although interactions between viral and host proteins have been studied extensively, little is known about how the vial genome may interact with the host genome and how such interactions could affect the activities of both the virus and the host cell. Since the three-dimensional organization of a genome can have significant impact on genomic activities such as transcription and replication, we hypothesize that such structure-based regulation of genomic functions also applies to viral genomes depending on their association with host genomic regions and their spatial locations inside the nucleus. Here, we used Tethered Chromosome Conformation Capture (TCC) to investigate viral-host genome interactions between the adenovirus and human lung fibroblast cells. We found viral-host genome interactions were enriched in certain active chromatin regions and chromatin domains marked by H3K27me3. The contacts by viral DNA seems to impact the structure and function of the host genome, leading to remodeling of the fibroblast epigenome. Our study represents the first comprehensive analysis of viral-host interactions at the genome structure level, revealing unexpectedly specific virus-host genome interactions. The non-random nature of such interactions indicates a deliberate but poorly understood mechanism for targeting of host DNA by foreign genomes.
MutS-Homolog2silencing generates tetraploid meiocytes in tomato (Solanum lycopersicum)
Authors: Sarma Supriya , Pandey Arun Kumar , Ravi Maruthachalam , Sreelakshmi Yellamaraju , Sharma Rameshwar
Published: May 2017

MSH2 is the core protein of MutS-homolog family involved in recognition and repair of the errors in the DNA. While other members of MutS-homolog family reportedly regulate mitochondrial stability, meiosis, and fertility, MSH2 is believed to participate mainly in mismatch repair. The search for polymorphism inMSH2sequence in tomato accessions revealed both synonymous and nonsynonymous SNPs; however, SIFT algorithm predicted that none of the SNPs influenced MSH2 protein function. The silencing ofMSH2gene expression by RNAi led to phenotypic abnormalities in highly-silenced lines, particularly in the stamens with highly reduced pollen formation.MSH2silencing exacerbated formation of UV-B induced thymine dimers and blocked light-induced repair of the dimers. TheMSH2silencing also affected the progression of male meiosis to a varying degree with either halt of meiosis at zygotene stage or formation of diploid tetrads. The immunostaining of male meiocytes with centromere localized CENPC (Centromere protein C) protein antibody showed the presence of 48 univalent along with 24 bivalent chromosomes suggesting abnormal tetraploid meiosis. The mitotic cells of root tips of silenced lines showed diploid nuclei but lacked intervening cell plates leading to cells with syncytial nuclei. Thus we speculate that tetraploid pollen mother cells may have arisen due to the fusion of syncytial nuclei before the onset of meiosis. It is likely that in addition to Mismatch repair (MMR), MSH2 may have an additional role in regulating ploidy stability.
RANKL signaling sustains primary tumor growth in genetically engineered mouse models of lung adenocarcinoma
Authors: Faget Julien , Contat Caroline , Zangger Nadine , Peters Solange , Meylan Etienne
Published: May 2017

Hypothesis

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality. Recent retrospective clinical analyses suggest that blocking the receptor activator of NF-κB (RANK) signaling pathway inhibits the growth of NSCLC and might represent a new treatment strategy.

Methods

RANKandRANKLexpression in human lung adenocarcinoma was interrogated from publicly available gene expression datasets. Several genetically engineered mouse models were used to evaluate treatment efficacy of RANK-Fc to block RANKL, with primary tumor growth measured longitudinally using micro-computed tomography. A combination of RANKL blockade with cisplatin was tested to mirror an ongoing clinical trial.

Results

In human lung adenocarcinoma datasets,RANKLexpression was associated with decreased survival andKRASmutation, with the highest levels in tumors with co-occurringKRASandLKB1mutations. InKrasLSL-G12D/WT, KrasLSL-G12D/WT;Lkb1Flox/FloxandKrasLSL-G12D/WT;p53Flox/Floxmouse models of lung adenocarcinoma, we monitored an impaired progression of tumors upon RANKL blockade. Despite elevated expression of RANKL and RANK in immune cells, treatment response was not associated with major changes in the tumor immune microenvironment. Combined RANK-Fc with cisplatin revealed increased efficacy compared to single agents.

Conclusions

RANKL blocking agents impair the growth of primary lung tumors in several mouse models of lung adenocarcinoma, and suggest that patients withKRASmutant lung tumors will benefit from such treatments.
In situ genotyping of a pooled strain library after characterizing complex phenotypes
Authors: Lawson Michael J. , Camsund Daniel , Larsson Jimmy , Baltekin Özden , Fange David , Elf Johan
Published: May 2017

So far, it has not been possible to perform advanced microscopy on pool generated strain libraries and at the same time know each strain’s genotype. We have overcome this barrier by identifying the genotypes for individual cellsin situafter a detailed characterization of the phenotype. The principle is demonstrated by single molecule fluorescence imaging ofE. colistrains harboring barcoded plasmids that express a sgRNA which suppress different genes through dCas9.
Postmitotic separation enables selective niche retention of one daughter cell in intestinal crypts and is facilitated by interkinetic nuclear migration and basal tethering
Authors: Carroll Thomas D. , Langlands Alistair J. , Osborne James M. , Newton Ian P. , Appleton Paul L. , Näthke Inke
Published: May 2017

Homeostasis of renewing tissues requires balanced proliferation, differentiation and movement. This is particullary important in the intestinal epithelium where lineage tracing suggests that stochastic differentiation choices are intricately coupled to position. To determine how position is achieved we followed proliferating cells in intestinal organoids and discovered that behaviour of mitotic sisters predicted long-term positioning. Normally, 70% of sisters remain neighbours while 30% lose contact separating after cytokinesis. Postmitotic placements predict differences in positions of sisters later: adjacent sisters reach similar positions; one separating sister remains close to its birthplace, the other moves upward. Computationally modelling crypt dynamics confirmed post-mitotic separation as a mechanism for placement of sisters into different niches. Separation depends on interkinetic nuclear migration, cell size, and asymmetric tethering by a basal process. These processes are altered whenAdenomatous polyposis coli(Apc) is mutant and separation is lost. We conclude that post-mitotic placement enables stochastic niche exit and when defective, supports the clonal expansion ofApcmutant cells.
A face identity hallucination (palinopsia) generated by intracerebral stimulation of the face-selective right lateral fusiform cortex
Authors: Jonas Jacques , Brissart Hélène , Hossu Gabriela , Colnat-Coulbois Sophie , Vignal Jean-Pierre , Rossion Bruno , Maillard Louis
Published: May 2017

We report the case of a patient (MB, young female human subject) who systematically experiences confusion between perceived facial identities when electrically stimulated inside the lateral section of the right fusiform gyrus. In the presence of a face stimulus (an experimenter or a photograph), intracerebral electrical stimulation in this region generates a perceptual hallucination of an individual facial part integrated within the whole perceived face, i.e. facial palinopsia. In the presence of a distracting stimulus (visual scene or object picture), the patient also experiences an individual face percept superimposed on the non-face stimulus. The stimulation site evoking this category-selective transient palinopsia is localized in a region showing highly selective responses to faces both with functional magnetic resonance imaging (“Fusiform Face Area”, “FFA”) and intracerebral electrophysiological recordings during fast periodic visual stimulation (FPVS). Importantly, the largest electrophysiological response to fast periodic changes of facial identity is also found at this location. Altogether, these observations suggest that a local face-selective region of the right lateral fusiform gyrus suffices to generate a vivid percept of an individual face, supporting the active role of this region in individual face representation.
A reagentless biosensor for mRNA: a new tool to study transcription
Authors: Cook Alexander , Hari-Gupta Yukti , Toseland Christopher P.
Published: May 2017

Gene expression, catalysed by RNA polymerases, is one of the most fundamental processes in living cells. Yet, the means to study their activity are currently limited. The majority of methods to quantify mRNA are based upon initial purification of the nucleic acid. This leads to experimental inaccuracies and loss of product. Here, we describe the use of a reagentless mRNA fluorescent biosensor based upon the single stranded binding (SSB) protein. In this study, SSB showed similar binding properties to mRNA, to that of its native substrate, ssDNA. Furthermore, fluorescently labelled MDCC-SSB gave the same fluorescence response with both ssDNA and ssRNA, in a concentration dependent manner. When directly compared to RT-qPCR, we found the biosensor to be more reproducible with no product lost through purification. Therefore, the MDCC-SSB is a novel tool for comparative measurement of mRNA yield followingin vitrotranscription.
Analysis and correction of compositional bias in sparse sequencing count data
Authors: Kumar M. Senthil , Slud Eric V. , Okrah Kwame , Hicks Stephanie C. , Hannenhalli Sridhar , Bravo Héctor Corrada
Published: May 2017

Count data derived from high-throughput DNA sequencing is frequently used in quantitative molecular assays. Due to properties inherent to the sequencing process, unnormalized count data is compositional, measuring relative and not absolute abundances of the assayed features. This compositional bias confounds inference of absolute abundances. We demonstrate that existing techniques for estimating compositional bias fail with sparse metagenomic 16S count data and propose an empirical Bayes normalization approach to overcome this problem. In addition, we clarify the assumptions underlying frequently used scaling normalization methods in light of compositional bias, including scaling methods that were not designed directly to address it.
Sleep Benefits Memory for Semantic Category Structure While Preserving Exemplar-Specific Information
Authors: Schapiro Anna C. , McDevitt Elizabeth A. , Chen Lang , Norman Kenneth A. , Mednick Sara C. , Rogers Timothy T.
Published: May 2017

Semantic memory encompasses knowledge about both the properties that typify concepts (e.g. robins, like all birds, have wings) as well as the properties that individuate conceptually related items (e.g. robins, in particular, have red breasts). We investigate the impact of sleep on new semantic learning using a property inference task in which both kinds of information are initially acquired equally well. Participants learned about three categories of novel objects possessing some properties that were shared among category exemplars and others that were unique to an exemplar, with exposure frequency varying across categories. In Experiment 1, memory for shared properties improved and memory for unique properties was preserved across a night of sleep, while memory for both feature types declined over a day awake. In Experiment 2, memory for shared properties improved across a nap, but only for the lower-frequency category, suggesting a prioritization of weakly learned information early in a sleep period. The increase was significantly correlated with amount of REM, but was also observed in participants who did not enter REM, suggesting involvement of both sleep stages. The results provide the first evidence that sleep improves memory for the shared structure of object categories, while simultaneously preserving object-unique information.
Two Novel Bioactive Peptides from Antarctic Krill with Dual Angiotensin Converting Enzyme and Dipeptidyl Peptidase IV Inhibitory Activities
Authors: Ji Wei , Zhang Chaohua , Ji Hongwu
Published: May 2017

Inhibition of dipeptidyl peptidase IV (DPP‐IV) and angiotensin converting enzyme (ACE) are considered useful in managing 2 often associated conditions: diabetes and hypertension. In this study, corolase PP was used to hydrolyze Antarctic krill protein. The hydrolysate (AKH) was isolated by ultrafiltration and purified by size‐exclusion chromatography, ion exchange chromatography and reversed‐phase high‐performance liquid chromatography (RP‐HPLC) sequentially. The in vitro inhibitory activities of all AKHs and several fractions obtained against ACE and DPP‐IV were assessed. Two peptides, purified with dual‐strength inhibitory activity against ACE and DPP‐IV, were identified by TOF‐MS/MS. Results indicated that not all fractions exhibited dual inhibitory activities of ACE and DPP‐IV. The purified peptide Lys‐Val‐Glu‐Pro‐Leu‐Pro had half‐maximal inhibitory concentrations (IC50) of 0.93±0.05 and 0.73±0.04 mg/mL against ACE and DPP‐IV, respectively. The other peptide Pro‐Ala‐Leu had IC50 values of 0.64±0.05 and 0.88±0.03 mg/mL against ACE and DPP‐IV, respectively. This study firstly reported the sequences of dual bioactive peptides from Antarctic krill proteins, further provided new insights into the bioactive peptides responsible for the ACE and DPP‐IV inhibitory activities from the Antarctic krill protein hydrolysate to manage hypertension and diabetes.
Inhibitor‐Assisted High‐Pressure Inactivation of Bacteria in Skim Milk
Authors: Liu Hai‐bin , Li Ping , Sun Chang , Du Xin‐jun , Zhang Yan , Wang Shuo
Published: May 2017

The combined inactivation effects of high hydrostatic pressure (HHP) and antimicrobial compounds (potassium sorbate and ε‐polylysine [ε‐PL]) on 4 different bacterial strains present in skim milk and the effect of these treatments on milk quality were investigated in this study. HHP treatment at 500 MPa for 5 min reduced the populations of Escherichia coli, Salmonella enterica Typhimurium, Listeria monocytogenes, and Staphylococcus aureus from 6.5 log colony‐forming units (CFUs) or higher to less than 1 log CFU/mL. Compared to HHP alone, HHP with potassium or ε‐PL resulted in significantly higher reductions in the bacterial counts. After 5 min of treatment with HHP (500 MPa) and ε‐PL (2 mg/mL), no growth of E. coli, S. enterica Typhimurium, or L. monocytogenes in skim milk was observed during 15 d of refrigerated storage (4 ± 1 °C). Scanning electron microscopy analysis revealed that the synergistic treatments caused more serious damage to the bacterial cell walls. Quality assessments of the treated samples indicated that the combined treatments did not influence the color, the turbidity, the concentrations of –SH group of the proteins, or the in vitro digestion patterns of the milk. This study demonstrates that HHP with potassium or ε‐PL may be useful in the processing of milk or milk‐containing foods.
The Influence of pH and Sodium Hydroxide Exposure Time on Glucosamine and Acrylamide Levels in California‐Style Black Ripe Olives
Authors: Charoenprasert Suthawan , Zweigenbaum Jerry A. , Zhang Gong , Mitchell Alyson E.
Published: May 2017

Acrylic acid, N‐acetyl‐glucosamine and glucosamine were investigated for their role in the formation of acrylamide in California‐style black ripe olives [CBROs]. Levels of acrylic acid and glucosamine are reported for the first time in fresh (333.50 ± 21.88 and 243.59 ± 10.06 nmol/g, respectively) and in brine‐stored olives (184.50 ± 6.02 and 165.88 ± 11.51 nmol/g, respectively). Acrylamide levels significantly increased when acrylic acid (35.2%), N‐acetyl‐glucosamine (29.9%), and glucosamine (124.0%) were added to olives prior to sterilization. However, isotope studies indicate these compounds do not contribute carbon and/or nitrogen atoms to acrylamide. The base‐catalyzed degradation of glucosamine is demonstrated in olive pulp and a strong correlation (r2 = 0.9513) between glucosamine in olives before sterilization and acrylamide formed in processed CBROs is observed. Treatment with sodium hydroxide (pH > 12) significantly reduces acrylamide levels over 1 to 5 d without impacting olive fruit texture.
Characterization of Sodium Mobility and Binding by 23Na NMR Spectroscopy in a Model Lipoproteic Emulsion Gel for Sodium Reduction
Authors: Okada Kyle S. , Lee Youngsoo
Published: May 2017

The effects of formulation and processing parameters on sodium availability in a model lipid/protein‐based emulsion gel were studied for purposes of sodium reduction. Heat‐set model gels were prepared with varying levels of protein, lipid, and NaCl contents and high pressure homogenization treatments. Single quantum and double quantum‐filtered 23Na NMR spectroscopy experiments were used to characterize sodium mobility, structural order around “bound” (restricted mobility) sodium, and sodium binding, which have been correlated to saltiness perception in food systems previously. Total sodium mobility was lower in gels with higher protein or fat content, and was not affected by changes in homogenization pressure. The gels with increased protein, fat, or homogenization pressure had increased structure surrounding “bound” sodium and more relative “bound” sodium due to increased interfacial protein interactions. The data obtained in this study provide information on factors affecting sodium availability, which can be applied towards sodium reduction in lipid/protein‐based foods.
Sending family history questionnaires to patients before a colonoscopy improves genetic counseling for hereditary colorectal cancer
Authors: Kessels Koen , Eisinger Joey D , Letteboer Tom G , Offerhaus G Johan A , Siersema Peter D , Moons Leon M G
Published: May 2017

OBJECTIVES

To investigate whether sending a family history questionnaire to patients prior to undergoing colonoscopy results in an increased availability of family history and better genetic counseling.

METHODS

A questionnaire was mailed to patients before they underwent outpatient colonoscopy at a university hospital in 2013. These patients’ additional characteristics and referral for genetic evaluation were retrieved from the electronic medical records. Patients undergoing inpatient coloboscopy, with confirmed hereditary colorectal cancer (CRC) or inflammatory bowel disease were excluded. All study patients from 2010 to 2013 were matched with the database of the genetics department to determine who consulted a geneticist.

RESULTS

A total of 6163 patients underwent colonoscopy from 2010 to 2013. Of 1421 who underwent colonoscopy in 2013, 53 (3.7%) consulted a geneticist, while 75 (1.6%) of 4742 patients undergoing colonoscopy between 2010 and 2012 did so (P < 0.01). A total of 974 patients undergoing colonoscopy in 2013 were included to evaluate the completed questionnaire. Of these, 282 (29.0%) completed the questionnaire. Family history was not recorded in the electronic medical records of 393 (40.3%). In 129 (32.8%), family history was obtained from the completed questionnaire. In 2013, 49 (60.5%) out of 81 patients referred for genetic counseling were referred based on their family history. Eight (9.9%) patients were referred based on the completed questionnaire.

CONCLUSION

Screening for hereditary CRC in a population undergoing outpatient colonoscopy with a questionnaire sent by mail resulted in an increased availability of family histories and genetic counseling.
Exploring bacterial interspecific interactions for discovery of novel antimicrobial compounds
Authors: Tyc Olaf , de Jager Victor C.L. , van den Berg Marlies , Gerards Saskia , Janssens Thierry K.S. , Zaagman Niels , Kai Marco , Svatos Ales , Zweers Hans , Hordijk Cornelis , Besselink Harrie , de Boer Wietse , Garbeva Paolina
Published: May 2017

Recent studies indicated that the production of secondary metabolites by soil bacteria can be triggered by interspecific interactions. However, little is known to date about interspecific interactions between Gram‐positive and Gram‐negative bacteria. In this study, we aimed to understand how the interspecific interaction between the Gram‐positive Paenibacillus sp. AD87 and the Gram‐negative Burkholderia sp. AD24 affects the fitness, gene expression and the production of soluble and volatile secondary metabolites of both bacteria. To obtain better insight into this interaction, transcriptome and metabolome analyses were performed. Our results revealed that the interaction between the two bacteria affected their fitness, gene expression and the production of secondary metabolites. During interaction, the growth of Paenibacillus was not affected, whereas the growth of Burkholderia was inhibited at 48 and 72 h. Transcriptome analysis revealed that the interaction between Burkholderia and Paenibacillus caused significant transcriptional changes in both bacteria as compared to the monocultures. The metabolomic analysis revealed that the interaction increased the production of specific volatile and soluble antimicrobial compounds such as 2,5‐bis(1‐methylethyl)‐pyrazine and an unknown Pederin‐like compound. The pyrazine volatile compound produced by Paenibacillus was subjected to bioassays and showed strong inhibitory activity against Burkholderia and a range of plant and human pathogens. Moreover, strong additive antimicrobial effects were observed when soluble extracts from the interacting bacteria were combined with the pure 2,5‐bis(1‐methylethyl)‐pyrazine. The results obtained in this study highlight the importance to explore bacterial interspecific interactions to discover novel secondary metabolites and to perform simultaneously metabolomics of both, soluble and volatile compounds.
Identification of tissue‐specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics
Authors: Barger Jamie L. , Vann James M. , Cray Nicole L. , Pugh Thomas D. , Mastaloudis Angela , Hester Shelly N. , Wood Steven M. , Newton Michael A. , Weindruch Richard , Prolla Tomas A.
Published: May 2017

Caloric restriction (CR) without malnutrition has been shown to retard several aspects of the aging process and to extend lifespan in different species. There is strong interest in the identification of CR mimetics (CRMs), compounds that mimic the beneficial effects of CR on lifespan and healthspan without restriction of energy intake. Identification of CRMs in mammals is currently inefficient due to the lack of screening tools. We have performed whole‐genome transcriptional profiling of CR in seven mouse strains (C3H/HeJ, CBA/J, DBA/2J, B6C3F1/J, 129S1/SvImJ, C57BL/6J, and BALB/cJ) in white adipose tissue (WAT), gastrocnemius muscle, heart, and brain neocortex. This analysis has identified tissue‐specific panels of genes that change in expression in multiple mouse strains with CR. We validated a subset of genes with qPCR and used these to evaluate the potential CRMs bezafibrate, pioglitazone, metformin, resveratrol, quercetin, 2,4‐dinitrophenol, and L‐carnitine when fed to C57BL/6J 2‐month‐old mice for 3 months. Compounds were also evaluated for their ability to modulate previously characterized biomarkers of CR, including mitochondrial enzymes citrate synthase and SIRT3, plasma inflammatory cytokines TNF‐α and IFN‐γ, glycated hemoglobin (HbA1c) levels and adipocyte size. Pioglitazone, a PPAR‐γ agonist, and L‐carnitine, an amino acid involved in lipid metabolism, displayed the strongest effects on both the novel transcriptional markers of CR and the additional CR biomarkers tested. Our findings provide panels of tissue‐specific transcriptional markers of CR that can be used to identify novel CRMs, and also represent the first comparative molecular analysis of several potential CRMs in multiple tissues in mammals.
A new methodological approach to adjust alcohol exposure distributions to improve the estimation of alcohol‐attributable fractions
Authors: Parish William J. , Aldridge Arnie , Allaire Benjamin , Ekwueme Donatus U. , Poehler Diana , Guy Gery P. , Thomas Cheryll C. , Trogdon Justin G.
Published: May 2017

Background and Aims

To assess the burden of excessive alcohol use, researchers estimate alcohol‐attributable fractions (AAFs) routinely. However, under‐reporting in survey data can bias these estimates. We present an approach that adjusts for under‐reporting in the estimation of AAFs, particularly within subgroups. This framework is a refinement of a previous method conducted by Rehm et al.

Methods

We use a measurement error model to derive the ‘true’ alcohol distribution from a ‘reported’ alcohol distribution. The ‘true’ distribution leverages per‐capita sales data to identify the distribution average and then identifies the shape of the distribution with self‐reported survey data. Data are from the National Alcohol Survey (NAS), the National Household Survey on Drug Abuse (NHSDA) and the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). We compared our approach with previous approaches by estimating the AAF of female breast cancer cases.

Results

Compared with Rehm et al.’s approach, our refinement performs similarly under a gamma assumption. For example, among females aged 18–25 years, the two approaches produce estimates from NHSDA that are within a percentage point. However, relaxing the gamma assumption generally produces more conservative evidence. For example, among females aged 18–25 years, estimates from NHSDA based on the best‐fitting distribution are only 19.33% of breast cancer cases, which is a much smaller proportion than the gamma‐based estimates of approximately 28%.

Conclusions

A refinement of Rehm et al.’s approach to adjusting for underreporting in the estimation of alcohol‐attributable fractions provides more flexibility. This flexibility can avoid biases associated with failing to account for the underlying differences in alcohol consumption patterns across different study populations. Comparisons of our refinement with Rehm et al.’s approach show that results are similar when a gamma distribution is assumed. However, results are appreciably lower when the best‐fitting distribution is chosen versus gamma‐based results.
Variation in cannabis potency and prices in a newly legal market: evidence from 30 million cannabis sales in Washington state
Authors: Smart Rosanna , Caulkins Jonathan P. , Kilmer Beau , Davenport Steven , Midgette Greg
Published: May 2017

Aims

To (1) assess trends and variation in the market share of product types and potency sold in a legal cannabis retail market and (2) estimate how potency and purchase quantity influence price variation for cannabis flower.

Design

Secondary analysis of publicly available data from Washington State's cannabis traceability system spanning 7 July 2014 to 30 September 2016. Descriptive statistics and linear regressions assessed variation and trends in cannabis product variety and potency. Hedonic regressions estimated how purchase quantity and potency influence cannabis flower price variation.

Setting

Washington State, USA.

Participants

(1) A total of 44 482 176 million cannabis purchases, including (2) 31 052 123 cannabis flower purchases after trimming price and quantity outliers.

Measurements

Primary outcome measures were (1) monthly expenditures on cannabis, total delta‐9‐tetrahydrocannabinol (THC) concentration and cannabidiol (CBD) concentration by product type and (2) excise tax‐inclusive price per gram of cannabis flower. Key covariates for the hedonic price regressions included quantity purchased, THC and CBD.

Findings

Traditional cannabis flowers still account for the majority of spending (66.6%), but the market share of extracts for inhalation increased by 145.8% between October 2014 and September 2016, now comprising 21.2% of sales. The average THC‐level for cannabis extracts is more than triple that for cannabis flowers (68.7% compared to 20.6%). For flower products, there is a statistically significant relationship between price per gram and both THC [coefficient = 0.012; 95% confidence interval (CI) = 0.011–0.013] and CBD (coefficient = 0.017; CI = 0.015–0.019). The estimated discount elasticity is −0.06 (CI = −0.07 to −0.05).

Conclusions

In the state of Washington, USA, the legal cannabis market is currently dominated by high‐THC cannabis flower, and features growing expenditures on extracts. For cannabis flower, both THC and CBD are associated with higher per‐gram prices, and there are small but significant quantity discounts.
The contribution of alcohol use and other behavioural, material and social factors to socio‐economic differences in alcohol‐related disorders in a Swedish cohort
Authors: Sydén Lovisa , Sidorchuk Anna , Mäkelä Pia , Landberg Jonas
Published: May 2017

Aims

We estimated the degree to which the relationship between socio‐economic position (SEP) and alcohol‐related disorders is attenuated after adjustment for levels and patterns of drinking, behavioural, material and social factors.

Design

A longitudinal cohort study with baseline in 2002, with linkage to register data on patient care and deaths in 2002–11 to yield the outcome measures.

Setting

Stockholm County, Sweden.

Participants

Respondents to baseline survey aged 25–64 (n = 17 440) with information on all studied covariates.

Measurements

Occupational class was the studied SEP indicator and a combined measure of volume of weekly alcohol consumption and frequency of heavy episodic drinking, smoking, employment status, income, social support, marital status and education, all at baseline, were the studied covariates. Alcohol‐related disorders (n = 388) were indicated by first register entries on alcohol‐related medical care or death during the follow‐up.

Findings

Unskilled workers had an approximately four times greater risk of alcohol‐related disorders than higher non‐manual employees, hazard ratio (HR) = 4.08 (2.78, 5.98). After adjustment for alcohol use, the SEP difference in risk for alcohol‐related harm fell by a fourth for the same group, HR = 2.91 (1.96, 4.33). The difference was reduced further when behavioural factors and material factors were taken into account, HR = 2.09 (1.34, 3.26), whereas adjusting for social factors and attained education resulted in smaller reductions.

Conclusions

Socio‐economic differences in alcohol use explain one fourth of the socio‐economic position differences in alcohol‐related disorders in Stockholm, Sweden. Hazardous alcohol use and other behavioural, material and social factors together explain nearly 60% of the socio‐economic position differences in alcohol‐related disorders.
Familial association of abstinent remission from alcohol use disorder in first‐degree relatives of alcohol‐dependent treatment‐seeking probands
Authors: McCutcheon Vivia V. , Schuckit Marc A. , Kramer John R. , Chan Grace , Edenberg Howard J. , Smith Tom L. , Bender Annah K. , Hesselbrock Victor , Hesselbrock Michie , Bucholz Kathleen K.
Published: May 2017

Background and Aims

Studies that have included family history of alcohol use disorder (AUD) as a predictor of remission from AUD have yielded few significant results. The goals of this study were to estimate the association of persistent AUD, non‐abstinent remission and abstinent remission (‘AUD/remission status’) in a proband with AUD/remission status in a relative and to test whether this association differed in related and unrelated proband‐relative pairs.

Design

High‐risk family study of alcohol dependence. Probands were recruited from treatment settings and relatives were invited to participate. Baseline assessments occurred between 1991 and 1998 with follow‐up between 1996 and 2005. Half of probands were matched with a biological 1st‐degree relative with life‐time AUD (related group) and half of probands were paired with an unrelated individual with life‐time AUD (unrelated group).

Setting

Brooklyn, New York; Indianapolis, Indiana; Iowa City, Iowa; San Diego, California; Farmington, Connecticut; and St Louis, Missouri, USA.

Participants

A total of 606 probands (25.7% female, mean age 37.7) with baseline and follow‐up data and 606 of their 1st‐degree relatives who had life‐ime AUDs (45.8% female, mean age 36.2 years).

Measurements

Persistent AUD, non‐abstinent remission and abstinent remission were based on self‐report interview data on most recent AUD symptoms and alcohol consumption. Dependent variable was relatives’ AUD/remission status. Independent variable was probands’ AUD/remission status.

Findings

A total of 34.6% of probands and 20.6% of relatives were abstinent and 11.1% of probands and 22.8% of relatives were in non‐abstinent remission. AUD/remission status was correlated significantly in related (r = 0.23, P = 0.0037) but not in unrelated pairs. A significant interaction of probands’ abstinent remission with a variable representing related (versus unrelated, P = 0.003) pairs suggested a familial association for abstinent remission. In related pairs, individuals with an abstinent proband were more likely to be abstinent themselves than were individuals whose proband had persistent AUD [relative risk ratio = 3.27, 95% confidence interval (CI) = 1.56–6.85, P = 0.002]; this association was not significant in unrelated pairs.

Conclusions

The likelihood of abstinent remission among people with alcohol use disorder appears to be more than three times greater for individuals who are related to an abstinent proband versus those related to a proband with persistent alcohol use disorder.