bluuebunny/crossref_metadata_2025 huggingface dataset:
Could Activity Modifications Indicate Physical Decline Among Adults With Symptomatic Knee Osteoarthritis?
Authors: Lee Augustine C. , Bloch Rina M. , Harvey William F. , Driban Jeffrey B. , Price Lori Lyn , Han Xingyi , Wang Chenchen
Published: August 2017

Objectives

Mobility activity modifications indicate early functional losses that act as precursors to future declines among community-dwelling older adults. However, there is scarce evidence on whether activity modifications indicate poorer physical health among adults with symptomatic osteoarthritis, a major cause of disability. Our purpose was to investigate whether patient-reported mobility activity modifications indicated poorer physical health among adults with symptomatic knee osteoarthritis.

Design

Secondary cross-sectional analysis of randomized trial data was performed. Preclinical Disability Questionnaire was used to group participants into the following three categories: difficulty, modified, and no difficulty walking/stair climbing. Kruskal Wallis and χ2 tests were used to compare clinical factors across groups.

Results

Among 121 participants (median age = 60 yrs; 73% female; 60% white), less than 10% had modified walking/stair climbing. Compared with those with no walking difficulty, participants with modified walking had significantly less balance (P = 0.01) and global health (P = 0.01) as well as greater knee pain (P = 0.05) and physical disability (P = 0.04). Those with modified stair climbing had significantly smaller walking distances (P = 0.03) compared with those with no difficulty stair climbing.

Conclusions

Activity modifications may signal early impairments in physical health among people with symptomatic knee osteoarthritis. If confirmed, patient-reported activity modifications may enhance symptom evaluation in osteoarthritis and enable a better understanding of the disablement process.
Lactate and Immunosuppression in Sepsis
Authors: Nolt Benjamin , Tu Fei , Wang Xiaohui , Ha Tuanzhu , Winter Randi , Williams David L. , Li Chuanfu
Published: August 2017

Serum lactate levels are traditionally interpreted as a marker of tissue hypoxia and often used clinically as an indicator of severity and outcome of sepsis/septic shock. Interestingly, recent studies involving the effects of tumor-derived lactate suggest that lactate itself may have an immunosuppressive effect in its local environment. This finding adds to the recent advances in immunometabolism that shed light on the importance of metabolism and metabolic intermediates in the regulation of innate immune and inflammatory responses in sepsis. In this article, we summarize recent studies, showing that the activation of immune cells requires aerobic glycolytic metabolism and that lactate produced by aerobic glycolysis may play an immunosuppressive role in sepsis.
Compensatory Reserve Index: Performance of A Novel Monitoring Technology to Identify the Bleeding Trauma Patient
Authors: Johnson Michael C. , Alarhayem Abdul , Convertino Victor , Carter Robert , Chung Kevin , Stewart Ronald , Myers John , Dent Daniel , Liao Lilian , Cestero Ramon , Nicholson Susannah , Muir Mark , Schwacha Martin , Wampler David , DeRosa Mark , Eastridge Brian
Published: August 2017

Introduction:

Hemorrhage is one of the most substantial causes of death after traumatic injury. Standard measures, including systolic blood pressure (SBP), are poor surrogate indicators of physiologic compromise until compensatory mechanisms have been overwhelmed. Compensatory Reserve Index (CRI) is a novel monitoring technology with the ability to assess physiologic reserve. We hypothesized CRI would be a better predictor of physiologic compromise secondary to hemorrhage than traditional vital signs.

Methods:

A prospective observational study of 89 subjects meeting trauma center activation criteria at a single level I trauma center was conducted from October 2015 to February 2016. Data collected included demographics, SBP, heart rate, and requirement for hemorrhage-associated, life-saving intervention (LSI) (i.e., operation or angiography for hemorrhage, local or tourniquet control of external bleeding, and transfusion >2 units PRBC). Receiver-operator characteristic (ROC) curves were formulated and appropriate thresholds were calculated to compare relative value of the metrics for predictive modeling.

Results:

For predicting hemorrhage-related LSI, CRI demonstrated a sensitivity of 83% and a negative predictive value (NPV) of 91% as compared with SBP with a sensitivity to detect hemorrhage of 26% (P < 0.05) and an NPV of 78%. ROC curves generated from admission CRI and SBP measures demonstrated values of 0.83 and 0.62, respectively. CRI identified significant hemorrhage requiring potentially life-saving therapy more reliably than SBP (P < 0.05).

Conclusion:

The CRI device demonstrated superior capacity over systolic blood pressure in predicting the need for posttraumatic hemorrhage intervention in the acute resuscitation phase after injury.
Embracing the Potential of Play for Children on the Autism Spectrum
Authors: Gerber Sima
Published: August 2017

In this article, the breadth and depth of play as an integrating process for children with developmental challenges are explored. The fact that play is a source of developmental growth suggests that its role in intervention with children with language and communication disorders cannot be overstated. Several contemporary play-based intervention programs for children with autism spectrum disorders are briefly reviewed. Models of child development that emphasize developmental integration are discussed. Clinical vignettes, dilemmas, and scenarios illustrate how language interventions can be designed to address engagement and meaning, the foundations of language development. Finally, the role of the adult or the attuned play partner is considered relative to current thinking about the caregiver–child relationship.
Should Benzodiazepines and Anticonvulsants Be Used During Electroconvulsive Therapy?
Authors: Tang Victor M. , Pasricha Akash N. , Blumberger Daniel M. , Voineskos Daphne , Pasricha Suvercha , Mulsant Benoit H. , Daskalakis Zafiris J.
Published: August 2017

Objective

This study aims to investigate the clinical effects of benzodiazepines or anticonvulsant use during a course of electroconvulsive therapy (ECT).

Method

A case report study of a patient who received ECT with and without concomitant flurazepam and pregabalin is presented. The literature on the use of benzodiazepines and anticonvulsants during ECT is reviewed.

Results

A woman with treatment resistant depression received a course of ECT while taking flurazepam and pregabalin, but seizures were of short duration and symptomatic improvement was minimal. After discontinuation of flurazepam and pregabalin, a course of right unilateral ultrabrief ECT was associated with adequate seizures and remission of depression and suicidal ideation. Our literature review suggests that benzodiazepines decrease seizure duration, but most evidence shows no association with increased seizure threshold. One prospective RCT and 3 large retrospective studies found that benzodiazepines compromise the efficacy of unilateral but not bilateral ECT. Regarding anticonvulsants, several studies had varied and contradictory results on their effect on seizure duration and seizure threshold. Of the 2 large retrospective studies and 3 RCTs, only 1 retrospective study showed that anticonvulsants decrease the efficacy of ECT.

Conclusions

Judicious assessment of all medications used in combination with ECT is recommended. Overall, published studies suggest that benzodiazepines and anticonvulsants impact the clinical outcomes of ECT less than what would be expected given their pharmacologic effects. However, there are significant gaps in the literature, including a lack of study on suprathreshold stimulation of right unilateral ECT and the possibility of a greater effect with higher medication doses.
Causes and consequences of adult sex ratio imbalance in a historical U.S. population
Authors: Schacht Ryan , Smith Ken R.
Published: August 2017

The responsiveness of individuals to partner availability has been well-documented across the literature. However, there is disagreement regarding the direction of the consequences of sex ratio imbalance. Specifically, does an excess of males or females promote male–male mating competition? In an attempt to clarify the role of the adult sex ratio (ASR) on behaviour, here we evaluate both competing and complimentary expectations derived from theory across the social and biological sciences. We use data drawn from a historical, nineteenth century population in North America and target several life-history traits thought to be affected by partner availability: age at first birth, relationship status, completed fertility and longevity. Furthermore, we assess the role of various contributors to a population's ASR. We find that both the contributors to and consequences of sex ratio imbalance vary over time. Our results largely support predictions of greater male pairbond commitment and lesser male mating effort, as well as elevated bargaining power of women in response to female scarcity. After reviewing our findings, and others from across the literature, we highlight the need to adjust predictions in response to ASR imbalance by the: (i) culturally mediated mating arena, (ii) variable role of demographic inputs across time and place, (iii) constraints to behavioural outcomes across populations, and (iv) ability and accuracy of individuals to assess partner availability.

This article is part of the themed issue ‘Adult sex ratios and reproductive strategies: a critical re-examination of sex differences in human and animal societies’.
Adult sex ratios and their implications for cooperative breeding in birds
Authors: Komdeur Jan , Székely Tamás , Long Xiaoyan , Kingma Sjouke A.
Published: August 2017

Cooperative breeding is a form of breeding system where in addition to a core breeding pair, one or more usually non-breeding individuals provide offspring care. Cooperative breeding is widespread in birds, but its origin and maintenance in contemporary populations are debated. Although deviations in adult sex ratio (ASR, the proportion of males in the adult population) have been hypothesized to influence the occurrence of cooperative breeding because of the resulting surplus of one sex and limited availability of breeding partners, this hypothesis has not been tested across a wide range of taxa. By using data from 188 bird species and phylogenetically controlled analyses, we show that cooperatively breeding species have more male-biased ASRs than non-cooperative species. Importantly, ASR predicts helper sex ratio: in species with more male-biased ASR, helper sex ratio is also more male biased. We also show that offspring sex ratios do not predict ASRs, so that the skewed ASRs emerge during the period when individuals aim to obtain a breeding position or later during adulthood. In line with this result, we found that ASR (among both cooperatively and non-cooperatively breeding species) is inversely related to sex bias in dispersal distance, suggesting that the cost of dispersal is more severe for the further-dispersing sex. As females usually disperse further in birds, this explains the generally male-biased ASR, and in combination with benefits of philopatry for males, this probably explains why ASR is more biased in cooperatively breeding species. Taken together, our results suggest that a sex bias in helping in cooperatively breeding species relates to biased ASRs. We propose that this relationship is driven by sex-specific costs and benefits of dispersal and helping, as well as other demographic factors. Future phylogenetic comparative and experimental work is needed to establish how this relationship emerges.

This article is part of the themed issue ‘Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies’.
Social determinants of adult sex ratios and racial/ethnic disparities in transmission of HIV and other sexually transmitted infections in the USA
Authors: Pouget Enrique Rodriguez
Published: August 2017

In Black population centres in the USA, adult sex ratios (ASRs) are strongly female-biased primarily due to high male incarceration and early mortality rates. I explore the system of social determinants that shape these ASRs, and describe their apparent consequences. Evidence suggests that female-biased ASRs play a role, along with racial residential segregation, to increase mixing between core and peripheral members of sexual networks, facilitating transmission of human immunodeficiency virus and other sexually transmitted infections. Unique historical factors underlie Black male incarceration and mortality rates in the USA, making comparisons with other groups or other countries challenging.

This article is part of the themed issue ‘Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies’.
High sex ratios in rural China: declining well-being with age in never-married men
Authors: Zhou Xudong , Hesketh Therese
Published: August 2017

In parts of rural China male-biased sex ratios at birth, combined with out-migration of women, have led to highly male-biased adult sex ratios, resulting in large numbers of men being unable to marry, in a culture where marriage and reproduction are an expectation. The aim of this study was to test the hypotheses that older unmarried men are more predisposed to depression, low self-esteem and aggression than both those who are married, and those who are younger and unmarried. Self-completion questionnaires were administered among men aged 20–40 in 48 villages in rural Guizhou province, southwestern China. Tools used included the Beck Depression Inventory, the Rosenberg's Self-esteem Scale and the Bryant-Smith Aggression Questionnaire. Regression models assessed psychological wellbeing while adjusting for socio-demographic variables. Completed questionnaires were obtained from 957 never-married men, 535 married men aged 30–40, 394 partnered men and 382 unpartnered men aged 20–29. After adjusting for socio-demographic variables, never-married men were more predisposed to depression (
p
< 0.05), aggression (
p
< 0.01), low self-esteem (
p
< 0.05) and suicidal tendencies (
p
< 0.001). All the psychological measures deteriorated with age in never-married men. In contrast, married men remained stable on these dimensions with age. Never-married men are a psychologically highly vulnerable group in a society where marriage is an expectation. Since the highest birth sex–ratio cohorts have not yet reached reproductive age, the social tragedy of these men will last for at least another generation.

This article is part of the themed issue ‘Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies’.
Climate-driven shifts in adult sex ratios via sex reversals: the type of sex determination matters
Authors: Bókony Veronika , Kövér Szilvia , Nemesházi Edina , Liker András , Székely Tamás
Published: August 2017

Sex reversals whereby individuals of one genetic sex develop the phenotype of the opposite sex occur in ectothermic vertebrates with genetic sex-determination systems that are sensitive to extreme temperatures during sexual differentiation. Recent rises in global temperatures have led researchers to predict that sex reversals will become more common, resulting in the distortion of many populations' sex ratios. However, it is unclear whether susceptibility to climate-driven sex-ratio shifts depends on the type of sex determination that varies across species. First, we show here using individual-based theoretical models that XX/XY (male-heterogametic) and ZZ/ZW (female-heterogametic) sex-determination systems can respond differentially to temperature-induced sex reversals. Interestingly, the impacts of climate warming on adult sex ratio (ASR) depend on the effects of both genotypic and phenotypic sex on survival and reproduction. Second, we analyse the temporal changes of ASR in natural amphibian populations using data from the literature, and find that ASR shifted towards males in ZZ/ZW species over the past 60 years, but did not change significantly in XX/XY species. Our results highlight the fact that we need a better understanding of the interactions between genetic and environmental sex-determining mechanisms to predict the responses of ectotherms to climate change and the associated extinction risks.

This article is part of the themed issue ‘Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies’.
Demographic and genetic consequences of disturbed sex determination
Authors: Wedekind Claus
Published: August 2017

During sex determination, genetic and/or environmental factors determine the cascade of processes of gonad development. Many organisms, therefore, have a developmental window in which their sex determination can be sensitive to, for example, unusual temperatures or chemical pollutants. Disturbed environments can distort population sex ratios and may even cause sex reversal in species with genetic sex determination. The resulting genotype–phenotype mismatches can have long-lasting effects on population demography and genetics. I review the theoretical and empirical work in this context and explore in a simple population model the role of the fitness

v
yy

of chromosomally aberrant YY genotypes that are a consequence of environmentally induced feminization. Low

v
yy

is mostly beneficial for population growth. During feminization, low

v
yy

reduces the proportion of genetic males and hence accelerates population growth, especially at low rates of feminization and at high fitness costs of the feminization itself (i.e. when feminization would otherwise not affect population dynamics much). When sex reversal ceases, low

v
yy

mitigates the negative effects of feminization and can even prevent population extinction. Little is known about

v
yy

in natural populations. The available models now need to be parametrized in order to better predict the long-term consequences of disturbed sex determination.

This article is part of the themed issue ‘Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies’.
Feasibility of near-infrared spectroscopic observation for traditional fermented soybean production
Authors: Jeon Jae Hwan , Lee Seon Mi , Cho Rae Kwang
Published: August 2017

In this study, near infrared (NIR) spectroscopy known as a non-destructive analysis technique was applied to investigate peptide cleavage and consequent release of amino acids in soybean lumps as affected by its moisture content and incubation time during fermentation at 25 for 3 weeks. The NIR spectra of the soybean lump semi-dried and soaked in saline water showed that absorption intensity around 1,400 nm originating from hydrogen bonds of water decreased and absorption band shifted to 1,430 nm as moisture content decreased during incubation at 25 for 3 weeks. In addition, absorption around 2,050 nm which was assigned to amino groups increased as incubation time increased. NIR spectra data from 1,000 to 2,250 nm showed higher accuracy in the discriminant analysis between outside and inside parts of fermented soybean lumps than visible spectra result. NIR spectroscopy for the amino acid and moisture contents in traditional fermented soybean lumps showed relatively good accuracy with the multiple correlation coefficient (R2) of 0.91 and 0.81, respectively, and root mean square error of cross validation (RMSECv) of 0.23 and 0.83%, respectively, in partial least square regression (PLSR). These results indicate that NIR spectral observations could be applicable to control the fermentation process for preparation of soybean products.
Microbiological, physicochemical, and organoleptic evaluation of fresh-cut vegetables irradiated using X-rays
Authors: Moon Byeong-Geum , Song Beom-Seok , Park Jong-Heum , Kim Jae-Kyung , Park Ha-Young , Kim Dong-Ho , Son Eun-Joo , Im Don-Sun , Eun Jong-Bang
Published: August 2017

Microbiological, physicochemical, and organoleptic properties of fresh-cut vegetables (FVs), carrots, green peppers, cherry tomatoes, and paprika after X-ray irradiation were evaluated to verify food quality suitable for the immune-depressed patients. Total concentrations of aerobic bacteria in non-irradiated samples, except for cherry tomatoes, were 1.63-3.34 log CFU/g. Irradiation dose exceed 0.4 kGy was used for carrots and green peppers whereas the sterilization dose of 0.2 kGy was used for both cherry tomatoes and paprika. A dose of 0.4 kGy was tentatively determined as the minimum allowable dose for sterilization of the FVs, based on D10-values of X-ray irradiation (0.11-0.32 kGy) for Escherichia coli, Listeria monocytogenes, and Salmonella Typhimurium inoculated on the samples. With respect to the physiological properties, only hardness was significantly decreased as the absorbed dose increased; however, there were no significant differences in hardness of the sterilized samples using X-rays at 0.4 kGy compared with those of non-irradiated samples (p<0.05). Moreover, overall acceptance scores of the sterilized FVs were higher than 5.0 points on a 7-point scale, indicating a good organoleptic quality. In a survey on preference of hospitalized patients with cancer (n=50), the average scores for the sterilized FVs, except for carrots, were higher than 4.0 points. In conclusion, it is considered that the FVs, except for carrots, sterilized using X-rays at 0.4 kGy could be served to immune-depressed patients as hygienically safe foods with acceptable organoleptic properties.
Physicochemical and sensory properties of Yakhobak (Cucurbita maxima subsp. maxima) paste under different high pressure heating conditions
Authors: Park Bo-Ram , Kim Na-Jeong , Choi Su-Jeong , Han Gui-Jung , Kim Ha-Yun
Published: August 2017

For the production of Yakhobak (Cucurbita maxima subsp. maxima) paste under various heating conditions, we steamed Yakhobak for roughly 20 min, followed by heating under high pressure treatment for 0 min (HHP0), 20 min (HHP20), 40 min (HHP40), and 60 min (HHP60). The physicochemical and sensory characteristics were subsequently investigated. Generally, no significant difference was observed in organic acid content and sensory characteristics score between Yakhobak paste treated with and without high-pressure heating. However, there was a significant difference in color value, soluble solids, and free sugar content. The L value for color of the group HHP0, untreated control Yakhobak paste (no high-pressure heating), decreased as time increased from 20 min to 60 min, with L values of 44.33, 44.25, and 42.86, respectively. The b value for the color of Yakhobak paste also decreased, showing a significant difference. Soluble solids and free sugar (fructose, glucose, sucrose) contents of the high-pressure heat-treated groups HHP20, HHP40, and HHP60 decreased compared with untreated group HHP0. Organic acid composition of Yakhobak paste included citric acid, malic acid, and fumaric acid, and the major organic acid was malic acid. Sensory score of HHP40 was the highest among all experimental groups in terms of overall preference, but there was no significant difference.
Optimization of blue berry extraction for beverage production using enzyme treatment
Authors: Ji Yu-Jeong , Im Moo-Hyeog
Published: August 2017

In this study, we tried to establish the best method for fresh blueberry beverage production using enzyme treatment as well as low temperature extraction. During extraction of physiologically functional materials, we used low temperature to prevent nutritional loss by heat. In addition, we investigated optimal blueberry extraction conditions using various enzyme treatments (cellulase, pectinase, cellulase:pectinase (1:1) mixture) to increase extraction efficiency and reduce turbidity. A variety and ratio of enzymes, extraction temperature, extraction time, and shaking speed were considered for the best extraction efficiency rate. We observed high extraction efficiency rates of 85.72-86.55% and 87.06-87.93%, respectively, upon cellulase or pectinase treatment. In addition, a mixture of cellulase:pectinase (1:1) showed an extraction efficiency rate of 86.84-88.14%. The best extraction efficiency rate was observed when crude blueberry was treated at 45°C (87.91%), for 3 h (87.88%), in a 90 rpm shaker (89.19%). Sugar content and acidity of blueberry extract were not affected by the various treatments. However, total phenolic compounds were detected upon pectinase treatment (18.62 mg/g). Only fructose and glucose as free sugars were found in all samples regardless of treatments and extraction conditions.
Effect of supercooling on the storage stability of rapidly frozen-thawed pork loins
Authors: Choi Eun Ji , Park Hae Woong , Chung Young Bae , Kim Jin Se , Park Seok Ho , Chun Ho Hyun
Published: August 2017

This study was performed to determine the rapid thawing method for reducing the thawing time of frozen pork loins and to examine the effects of supercooling on the microbiological, physicochemical, and sensory qualities of fresh and frozen-thawed pork during storage at -1.5, 4, and 15°C. Forced-air thawing at 4°C was the most time-consuming process, whereas radio frequency thawing time was the shortest by dielectric heating. The supercooling storage temperature was chosen to be -1.5°C because microstructural damages were not observed in the pork sample after cooling at -1.5°C for 24 h. Fresh or frozen-thawed pork loins stored at -1.5°C had lower drip loss and total volatile base nitrogen, thiobarbituric acid-reactive substance, and Hunter b* levels than loins stored at 4 and 15°C. In addition, the least degree of increase in preexisting microorganisms counts of the fresh or frozen-thawed pork loin samples was obtained during supercooled storage at -1.5°C. Sensory quality results of fresh and frozen-thawed pork loin samples stored at -1.5°C showed higher scores than the samples stored at 4 and 15°C. These data indicate that supercooling at -1.5°C in the meat processing industry would be effective for maintaining the quality of pork meats without ice crystal nucleation and formation.
Quality characteristics and biological activity of Yanggaeng with Glechoma hederacea var. longituba Nakai powder
Authors: Lim Su-Bin , Park Ki-Tae , Lee Eun-Ho , Kim Byung-Oh , Lee Seon-Ho , Kang In-Kyu , Cho Young-Je
Published: August 2017

The objective of this study is to investigate the quality characteristics of Yanggaeng by using the functional properties of Glechoma hederacea (GH). Sample was dried at 50°C dry oven. The results of the study were as follows : The Phenolic compounds of GH was 12.99±0.3 mg/g in water extract (GHWE), 3.14±0.07 mg/g in 70% ethanol extract (GHEE). The antioxidant activity of GH was determined in various phenolic concentrations at 50-200 μg/mL. DPPH activities of GHWE and GHEE were 77.16-78.24% and 73.04-77.00%, respectively. The ABTS were 84.35-99.75% and 83.74-99.55%. The anti-oxidant protection factor (PF) were 1.54-1.62 PF and 1.62-2.09 PF and TBARS were 42.93-94.09% and 91.05-95.19%, respectively. Tyrosinase inhibitory activity of GHEE increased concentration dependently. Hyaluronidase inhibition activity of GHEE and GHWE, showing that there were increasing pattern depending on the increases in the phenolics concentration of GH. In texture, Hardness and springiness were significantly different in the control and 2% groups, but cohesiveness and chewiness did not show any significant difference. In color, L value decreased in proportion to concentration, and a and b values did not change. Sensory characteristics showed that the 1% group had the highest score and the 2% group had the lowest score. Thus, when the GHP Yanggaeng was prepared, in consideration of its sensory characteristics, and at appropriate concentration on below 1%.
Antiproliferation effects of ethanol extract of garlic peels on human cancer cell lines
Authors: Son Dae-Yeul
Published: August 2017

Ethanol extract of garlic peels (GPE) was investigated for its antiproliferative effects on human cancer cell lines. Human lung cancer cell line A549 treated with 500 μg/mL GPE resulted in the growth inhibition of A549 by 90%. In stomach cancer cell AGS　proliferation inhibition activity, GPE showed 45% and 71% inhibition of AGS growth at 1,000 μg/mL and 2,000 μg/mL, respectively. GPE inhibited the growth of the breast cancer cells MCF-7 effectively at low concentration and showed 78% and 90% inhibitions of MCF-7 growth at 200 μg/mL and 500 μg/mL , respectively. GPE showed very significant antiproliferation effect on liver cancer cell line Hep3B and inhibited Hep3B cell growth by 57% at 100 μg/mL, and the inhibition’s rate increased up to 87% at 500 μg/mL. Antiproliferation effect of GPE on colorectal cancer cell HT-29 showed 15% reduction of HT-29 cell growth at 200 μg/mL and the growth rate was reduced in a dose dependent manner up to 1,000 μg/mL. These results indicated that GPE had high antiproliferation effects on breast and liver cancer cell lines at low concentrations (200 μg/mL), and by higher concentrations over 500 μg/mL, GPE inhibited the growth of A549 and HT-29. The results of our study suggested the potential use of garlic peels for use as an excellent antiproliferative substance for human cancer cells.
Reconsolidation-disruption diminishes spontaneous and stress-induced cocaine seeking
Authors: Marc TJ Exton-McGuinness , Mohamed L Drame , Charlotte R Flavell , Jonathan LC Lee
Published: August 2017

BACKGROUND

There has been a recent surge of interest in exploiting the process of reconsolidation to weaken maladaptive memories, in the hope this will drive the next wave of innovation in psychotherapy. Reconsolidation normally functions to stabilise and maintain memories in the long-term, and is critical in enabling memory updating. However, this process can be disrupted pharmacologically to weaken memories, or harnessed to allow destructive interference of a memory trace. Work has already begun to exploit this mechanism to disrupt pavlovian fear memories in the treatment of maladaptive anxiety and threat processing, and additionally being able to target instrumental memories may provide further clinical benefit.

METHODS

Expanding our rat intravenous (i.v.) self-administration paradigm, we tested whether disruption of instrumental memory reconsolidation with the noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 could reduce relapse of cocaine seeking in response to stress, drug-priming or presentation of a drug-associated cue.

RESULTS

Spontaneous responding for i.v. cocaine was reduced by reconsolidation-disruption. Furthermore, responding was not rescued by pharmacologically-induced stress. However, responding was restored following systemic administration of the drug, or presentation of a drug-associated cue.

CONCLUSIONS

These data are consistent with hypothesis that there exist multiple ‘routes to relapse’, and suggest that at least some of these routes could be blocked by reconsolidation-disruption. This work provides important proof-of-principle that reconsolidation based therapies are a viable means of reducing the rates of relapse in substance use disorders.
Cell cycle time series gene expression data encoded as cyclic attractors in Hopfield systems
Authors: Szedlak Anthony , Sims Spencer , Smith Nicholas , Paternostro Giovanni , Piermarocchi Carlo
Published: August 2017

Modern time series gene expression and other omics data sets have enabled unprecedented resolution of the dynamics of cellular processes such as cell cycle and response to pharmaceutical compounds. In anticipation of the proliferation of time series data sets in the near future, we use the Hopfield model, a recurrent neural network based on spin glasses, to model the dynamics of cell cycle in HeLa (human cervical cancer) andS. cerevisiaecells. We study some of the rich dynamical properties of these cyclic Hopfield systems, including the ability of populations of simulated cells to recreate experimental expression data and the effects of noise on the dynamics. Next, we use a genetic algorithm to identify sets of genes which, when selectively inhibited by local external fields representing gene silencing compounds such as kinase inhibitors, disrupt the encoded cell cycle. We find, for example, that inhibiting the set of four kinasesBRD4,MAPK1,NEK7, andYES1in HeLa cells causes simulated cells to accumulate in the M phase. Finally, we suggest possible improvements and extensions to our model.

Author Summary

Cell cycle – the process in which a parent cell replicates its DNA and divides into two daughter cells – is an upregulated process in many forms of cancer. Identifying gene inhibition targets to regulate cell cycle is important to the development of effective therapies. Although modern high throughput techniques offer unprecedented resolution of the molecular details of biological processes like cell cycle, analyzing the vast quantities of the resulting experimental data and extracting actionable information remains a formidable task. Here, we create a dynamical model of the process of cell cycle using the Hopfield model (a type of recurrent neural network) and gene expression data from human cervical cancer cells and yeast cells. We find that the model recreates the oscillations observed in experimental data. Tuning the level of noise (representing the inherent randomness in gene expression and regulation) to the “edge of chaos” is crucial for the proper behavior of the system. We then use this model to identify potential gene targets for disrupting the process of cell cycle. This method could be applied to other time series data sets and used to predict the effects of untested targeted perturbations.
dropClust: Efficient clustering of ultra-large scRNA-seq data
Authors: Sinha Debajyoti , Kumar Akhilesh , Kumar Himanshu , Bandyopadhyay Sanghamitra , Sengupta Debarka
Published: August 2017

Droplet based single cell transcriptomics has recently enabled parallel screening of tens of thousands of single cells. Clustering methods that scale for such high dimensional data without compromising accuracy are scarce. We exploit Locality Sensitive Hashing, an approximate nearest neighbor search technique to develop ade novoclustering algorithm for large-scale single cell data. On a number of real datasets, dropClust outperformed the existing best practice methods in terms of execution time, clustering accuracy and detectability of minor cell sub-types.
Ants express risk-adjusted sanitary care
Authors: Konrad Matthias , Pull Christopher D. , Seif Katharina , Metzler Sina , Grasse Anna V. , Cremer Sylvia
Published: August 2017

Being cared for when sick is a benefit of sociality that can reduce disease and improve survival of group members. However, individuals providing care risk contracting infectious diseases themselves. If they contract a low pathogen dose, they may develop micro-infections that do not cause disease, but still affect host immunity by either decreasing or increasing the host’s vulnerability to subsequent pathogen infections. Caring for contagious individuals can thus significantly alter the future disease susceptibility of caregivers. Using ants and their fungal pathogens as a model system, we here tested if the altered disease susceptibility of experienced caregivers, in turn, affects their expression of sanitary care behaviour. We found that micro-infections contracted during sanitary care had protective or neutral effects upon secondary exposure to the same (homologous) pathogen, but consistently induced high mortality upon super-infection with a different (heterologous) pathogen. In response to this risk, the ants selectively adjusted the expression of their sanitary care. Specifically, the ants performed less grooming yet more antimicrobial disinfection, when caring for nestmates contaminated with heterologous pathogens as compared to homologous ones. By modulating the components of sanitary care in this way, the ants reduced their probability of contracting super-infections of the harmful heterologous pathogens. The performance of risk-adjusted sanitary care reveals the remarkable capacity of ants to react to changes in their disease susceptibility, according to their own infection history, and to flexibly adjust collective care to individual risk.
The High-resolution Timeline of Expression of Ribosomal Protein Genes in Yeast
Authors: Li Xueling , Chen Gang , Fongang Bernard , Homouz Dirar , Rowicka Maga , Kudlicki Andrzej
Published: August 2017

The yeast ribosome is a complex molecular machine built from four rRNAs and over 70 r-proteins. Ribosome biogenesis involves ordered incorporation of ribosomal proteins, accompanied by and association and dissociation of other proteins specific to different stages of the process. By model-based analysis of temporal profiles of gene expression in a metabolically regulated system, we obtained an accurate, high-resolution estimation of the time of expression of genes coding for proteins involved in ribosome biogenesis. The ribosomal proteins are expressed in a sequence that spans approximately 25-minutes under metabolically regulated conditions. The genes coding for proteins incorporated into the mature ribosome are expressed significantly later than those that are not incorporated, but are otherwise involved in ribosome biogenesis, localization and assembly, rRNA processing and translational initiation. The relative expression time of proteins localized within specified neighborhood is significantly correlated with the distance to the centroid of the mature ribosome: protein localized closer to the center of mass of the entire complex tend to be expressed earlier than the protein localized further from the center. The timeline of gene expression also agrees with the known dependencies between recruitment of specific proteins into the mature ribosome. These findings are consistent in two independent experiments. We have further identified regulatory elements correlated with the time of regulation, including a possible dependence of expression time on the position of the RAP1 binding site within the 5’UTR.
Protein classification using modifiedn-gramandskip-grammodels
Authors: Islam S M Ashiqul , Heil Benjamin J , Kearney Christopher Michel , Baker Erich J
Published: August 2017

Motivation

Classification by supervised machine learning greatly facilitates the annotation of protein characteristics from their primary sequence. However, the feature generation step in this process requires detailed knowledge of attributes used to classify the proteins. Lack of this knowledge risks the selection of irrelevant features, resulting in a faulty model. In this study, we introduce a means of automating the work-intensive feature generation step via a Natural Language Processing (NLP)-dependent model, using a modified combination of N-Gram and Skip-Gram models (m-NGSG).

Results

A meta-comparison of cross validation accuracy with twelve training datasets from nine different published studies demonstrates a consistent increase in accuracy of m-NGSG when compared to contemporary classification and feature generation models. We expect this model to accelerate the classification of proteins from primary sequence data and increase the accessibility of protein prediction to a broader range of scientists.

Availability

m-NGSG is freely available at Bitbucket:https://bitbucket.org/smislam/mngsg/src

Supplements

link to supplementary documents

Contact

Erich_Baker@baylor.edu
Hidden diversity and macroevolutionary mode ofCaulimoviridaeuncovered by euphyllophyte paleoviruses
Authors: Gong Zhen , Han Guan-Zhu
Published: August 2017

Few viruses have been documented in plants outside angiosperms. Endogenous viral elements (paleoviruses) provide ‘molecular fossils’ for studying the deep history and macroevolution of viruses. Endogenous plant pararetroviruses (EPRVs) are widespread across angiosperms, but little is known about EPRVs in earlier branching plants. Here we use a large-scale phylogenomic approach to investigate the diversity and macroevolution of plant pararetroviruses (formally known asCaulimoviridae). We uncover an unprecedented and unappreciated diversity of EPRVs in the genomes of gymnosperms and ferns. The known angiosperm viruses only constitute a minor part of theCaulimoviridaediversity. By characterizing the distribution of EPRVs, we show that no major euphyllophyte lineages escape the activity ofCaulimoviridae, raising the possibility that many exogenousCaulimoviridaeremain to be discovered in euphyllophytes. We find that the copy numbers of EPRVs are generally high, suggesting that EPRVs define a unique group of repetitive elements and represent major components of euphyllophyte genomes. Phylogenetic analyses reveal an ancient monilophyte origin ofCaulimoviridaeand at least three independent origins ofCaulimoviridaein angiosperms by cross-division transmissions. Our findings uncover the remarkable diversity ofCaulimoviridaeand have important implications in understanding the origin and macroevolution of plant pararetroviruses.
Improving the quality of combined EEG-TMS neural recordings: Introducing the Coil Spacer
Authors: Ruddy K.L. , Woolley D.G. , Mantini D. , Balsters J.H. , Enz N. , Wenderoth N.
Published: August 2017

Background

In the last decade, interest in combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) approaches has grown substantially. Aside from the obvious artifacts induced by the magnetic pulses themselves, separate and more sinister signal disturbances arise as a result of contact between the TMS coil and EEG electrodes.

New method

Here we profile the characteristics of these artifacts and introduce a simple device – the coil spacer - to provide a platform allowing physical separation between the coil and electrodes during stimulation.

Results

EEG data revealed high amplitude signal disturbances when the TMS coil was in direct contact with the EEG electrodes, well within the physiological range of viable EEG signals. The largest artifacts were located in the Delta and Theta frequency range, and standard data cleanup using independent components analysis (ICA) was ineffective due to the artifact’s similarity to real brain oscillations.

Comparison with Existing Method

While the current best practice is to use a large coil holding apparatus to fixate the coil ‘hovering’ over the head with an air gap, the spacer provides a simpler solution that ensures this distance is kept constant throughout testing.

Conclusions

The results strongly suggest that data collected from combined TMS-EEG studies with the coil in direct contact with the EEG cap are polluted with low frequency artifacts that are indiscernible from physiological brain signals. The coil spacer provides a cheap and simple solution to this problem and is recommended for use in future simultaneous TMS-EEG recordings.
Activation of serotonin neurons promotes active exploitation in a probabilistic foraging task
Authors: Lottem Eran , Banerjee Dhruba , Vertechi Pietro , Sarra Dario , Lohuis Matthijs oude , Mainen Zachary F.
Published: August 2017

The neuromodulator serotonin (5-HT) has been implicated in a variety of functions that involve patience or impulse control. For example, activation of 5-HT neurons promotes waiting for delayed rewards. Many of these effects are consistent with a long-standing theory that 5-HT promotes behavioral inhibition, a motivational bias favoring passive over active behaviors. To further test this idea, we studied the impact of 5-HT in a probabilistic foraging task, in which mice must learn the statistics of the environment and infer when to leave a depleted foraging site for the next. Critically, mice were required to actively nose poke in order to exploit a given site. We found that optogenetic activation of 5-HT neurons in the dorsal raphe nucleus increased the willingness of mice to actively attempt to exploit a reward site before giving up. These results indicate that behavioral inhibition is not an adequate description of 5-HT function and suggest that a unified account must be based on a higher-order function.
From neurons to voxels - repetition suppression is best modelled by local neural scaling
Authors: Alink Arjen , Abdulrahman Hunar , Henson Richard N.
Published: August 2017

Inferring neural mechanisms from functional magnetic resonance imaging (fMRI) is challenging because the fMRI signal integrates over millions of neurons. One approach is to compare computational models that map neural activity to fMRI responses, to see which best predicts fMRI data. We used this approach to compare four possible neural mechanisms of fMRI adaptation to repeated stimuli (scaling, sharpening, repulsive shifting and attractive shifting), acting across three domains (global, local and remote). Six features of fMRI repetition effects were identified, both univariate and multivariate, from two independent fMRI experiments. After searching over parameter values, only the local scaling model could simultaneously fit all data features from both experiments. Thus fMRI stimulus repetition effects are best captured by down-scaling neuronal tuning curves in proportion to the difference between the stimulus and neuronal preference. These results emphasize the importance of formal modelling for bridging neuronal and fMRI levels of investigation.
Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier
Authors: Hoyles Lesley , Snelling Tom , Umlai Umm-Kulthum , Nicholson Jeremy K. , Carding Simon R. , Glen Robert C. , McArthur Simon
Published: August 2017

Background

Gut microbiota composition and function are symbiotically linked with host health, and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognized mechanisms exist by which the microbiome influences the gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesized interactions between circulating gut–derived microbial metabolites and the blood–brain barrier (BBB) also contribute to the gut–brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed.

Results

After demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 μM) on BBB propertiesin vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signaling.

Conclusions

Together, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut–brain axis that warrants further attention.
RAPID: Real-time image-based autofocus for all wide-field optical microscopy systems
Authors: Silvestri L. , Müllenbroich M. C. , Costantini I. , Di Giovanna A. P. , Sacconi L. , Pavone F. S.
Published: August 2017

Autofocus methods used in biomicroscopy are either based on the search of an optimal focus position – which requires suspending data collection during the optimization process – or on the continuous monitoring of the position of a fiducial plane – which may not coincide with the sample itself. Here, we introduce RAPID (Rapid Autofocus via Pupil-split Image phase Detection), a method for real-time image-based focus stabilization, applicable in all wide-field microscopy systems. We demonstrate that RAPID maintains high image quality in various settings, fromin vivofluorescence imaging to light-sheet microscopy. RAPID provides a universal autofocus solution for automated microscopy, and enables quantitative assays otherwise impossible in a standard microscope, such as 3D tracking of fast-moving organisms.