bluuebunny/crossref_metadata_2025 huggingface dataset:
L-3-n-butylphthalide soft capsules in the treatment of Parkinson disease dementia
Authors: Zhong Rui , Chen Qingling , Zhang Xinyue , Li Mengmeng , Lin Weihong
Published: June 2019

Background:

In recent years, L-3-n-butylphthalide (L-NBP) has been used for Parkinson disease dementia (PDD) to attenuate cognitive impairments in China. Therefore, we selected published and qualified clinical trials to conduct a systematic review and meta-analysis with the aim of assessing the effectiveness and safety of L-NBP in the treatment of PDD.

Objective:

This systematic review and meta-analysis aimed to assess the effectiveness and safety of L-NBP in the treatment of PDD.

Methods:

We searched PubMed, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP database), and Wan-Fang Database to collect eligible articles. We calculated pooled estimates of odds ratios or the standard mean deviation with 95% confidence intervals.

Results:

Eight randomized controlled trials were included in our meta-analysis. Our meta-analysis showed that L-NBP combined with Western medicine (WM) had a better effect on improving cognitive dysfunction, the total effective rate, symptoms of Parkinson disease (PD), and activities of daily living function than WM alone. Regarding safety, no serious adverse events were observed in the experimental group.

Conclusion:

We found that L-NBP as a complementary therapy may have a positive therapeutic effect for improving cognitive dysfunction, the total effective rate, symptoms of PD, quality of life, and the related serum factors in the treatment of PDD. Furthermore, L-NBP was a safe treatment for PDD. However, the findings of our meta-analysis may be influenced by the low quality of the included studies. We highlight the need to conduct trials with higher methodological quality.
Outcomes from different minimally invasive approaches for infected necrotizing pancreatitis
Authors: Hu Yong , Jiang Xun , Li Chunyan , Cui Yunfeng
Published: June 2019

Infected necrotizing pancreatitis (INP), the leading cause of mortality in the late phase of acute pancreatitis, nearly always requires intervention. In recent years minimal invasive surgery is becoming more and more popular for the management of INP, but few studies compared different minimally invasive strategies. The objective of this observation study was to evaluate the safety and effectiveness with several minimal invasive treatment.

We retrospectively reviewed cases of percutaneous catheter drainage (PCD), minimal access retroperitoneal pancreatic necrosectomy (MARPN), small incision pancreatic necrosectom (SIPN), single-incision access port retroperitoneoscopic debridement (SIAPRD) for INP between January 2013 and October 2018. Data were analyzed for the primary endpoints as well as secondary endpoints.

Eighty-one patients with INP were treated by minimally invasive procedures including PCD (n = 32), MARPN (n = 18), SIPN (n = 16), and SIAPRD (n = 15). Overall mortality was greatest after PCD 34% (MARPN 11% vs SIPN 6% vs SIRLD6%). Problems after initial surgery were ongoing sepsis (PCD 56% vs MARPN 50% vs SIPN 31% vs SIAPRD13%; P < .05). There was a significant difference in number of interventions (median, 6 vs 5 vs 3 vs 2; P < .05). Time from onset of symptoms to recovery was less for SIAPRD than for PCD, MARPN, or SIPN (median, 45 vs 102 vs 80 vs 67 days; P < .05).

SIAPRD remedy evidently improved outcomes, including systemic inflammatory response syndrome, number of interventions, length of hospital stay and overall cost. It is technically feasible, safe, and effective for INP, in contrast to others, and can achieve the best clinical results with the least cost. Furthermore, relevant multicentre randomized controlled trials are eager to prove these findings.
Innovations in kidney paired donation transplantation
Authors: D’Alessandro Thomas , Veale Jeffrey L.
Published: June 2019

Purpose of review

To analyze the innovations that have increased the reliability, convenience, and outcomes of kidney paired donation (KPD) that has led to thousands of living donor kidney transplants across the United States.

Recent findings

Over the past 10 years, KPD has grown over 200% on an annual basis. Though concerns had existed over cold ischemia time, research has shown that there is no correlation between travel time of a shipped kidney and the transplant outcome. The voucher program has started to continue to expand how to overcome obstacles to donation by solving the issue of a pair chronological incompatibility.

KPD is a relatively new field and the innovations it has spawned should continue to improve availability of high-quality living donor organs. The introduction of the family voucher should continue this trend.
Prevalence for and Factors Associated With Depression and Anxiety Symptoms in Mexican Patients With Rheumatoid Arthritis
Authors: Juárez-Rojop Isela Esther , Nolasco-Rosales German Alberto , Pérez-Mandujano Antonia , González-Castro Thelma Beatriz , Tovilla-Zárate Carlos Alfonso , López-Narváez María Lilia , Hernández-Nuñez Éufrates , Villar-Soto Mario , Fresan Ana
Published: June 2019

Background/Objective

It has been suggested that patients with rheumatoid arthritis (RA) often present depression and anxiety. The objective of this study was to estimate the prevalence of depression and anxiety symptoms in Mexican patients with RA and to determine associated factors of depression and anxiety in this population.

Methods

This was a cross-sectional study. We evaluated demographic characteristics, medical comorbidities, substance use, and disease characteristics in 103 patients with RA. Patients were enrolled from March 2016 to August 2017 The prevalence of depression and anxiety was estimated using the Hospital Anxiety and Depression Scale. We calculated the proportion of depression and anxiety symptoms and compared characteristics between groups. Finally, logistic regression model was used to determine the factors associated with depression and anxiety.

Results

Depression symptoms were present in 26.2% of patients, whereas anxiety symptoms were present in 16.5% of patients. Presence of hypertension was an associated factor with depression (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.06–9.23; p = 0.03). Low socioeconomic (OR, 3.78; 95% CI, 1.39–10.28; p = 0.009) and high scores of 28-joint Disease Activity Score were associated with anxiety (OR, 3.19; 95% CI, 1.20–8.45; p = 0.02).

Conclusions

Factor related to socioeconomic conditions, comorbid medical conditions, and disease activity were related to the presence of clinical depression and anxiety in Mexican patients with RA, which may have a negative impact in the course and outcome of the disease. We suggest an early identification of depression and anxiety in these patients through an early psychiatric evaluation.
The first formed tooth serves as a signalling centre to induce the formation of the dental row in zebrafish
Authors: Gibert Yann , Samarut Eric , Ellis Megan K. , Jackman William R. , Laudet Vincent
Published: June 2019

The diversity of teeth patterns in actinopterygians is impressive with tooth rows in many locations in the oral and pharyngeal regions. The first-formed tooth has been hypothesized to serve as an initiator controlling the formation of the subsequent teeth. In zebrafish, the existence of the first tooth (named 4 V1) is puzzling as its replacement is induced before the opening of the mouth. Functionally, it has been shown that 4 V1formation requires fibroblast growth factor (FGF) and retinoic acid (RA) signalling. Here, we show that the ablation of 4 V1prevents the development of the dental row demonstrating its dependency over it. If endogenous levels of FGF and RA are restored after 4 V1ablation, embryonic dentition starts again by de novo formation of a first tooth, followed by the dental row. Similarly, induction of anterior ectopic teeth induces subsequent tooth formation, demonstrating that the initiator tooth is necessary and sufficient for dental row formation, probably via FGF ligands released by 4 V1to induce the formation of subsequent teeth. Our results show that by modifying the formation of the initiator tooth it is possible to control the formation of a dental row. This could help to explain the diversity of tooth patterns observed in actinopterygians and more broadly, how diverse traits evolved through molecular fine-tuning.
Introduced parasite changes host phenotype, mating signal and hybridization risk:
Philornis downsi
effects on Darwin's finch song
Authors: Kleindorfer Sonia , Custance Georgina , Peters Katharina J. , Sulloway Frank J.
Published: June 2019

Introduced parasites that alter their host's mating signal can change the evolutionary trajectory of a species through sexual selection. Darwin's
Camarhynchus
finches are threatened by the introduced fly
Philornis downsi
that is thought to have accidentally arrived on the Galapagos Islands during the 1960s. The
P. downsi
larvae feed on the blood and tissue of developing finches, causing on average approximately 55% in-nest mortality and enlarged naris size in survivors. Here we test if enlarged naris size is associated with song characteristics and vocal deviation in the small tree finch (
Camarhynchus parvulus
), the critically endangered medium tree finch (
C. pauper
) and the recently observed hybrid tree finch group (
Camarhynchus
hybrids). Male
C. parvulus
and
C. pauper
with enlarged naris size produced song with lower maximum frequency and greater vocal deviation, but there was no significant association in hybrids. Less vocal deviation predicted faster pairing success in both parental species. Finally,
C. pauper
males with normal naris size produced species-specific song, but male
C. pauper
with enlarged naris size had song that was indistinguishable from other tree finches. When parasites disrupt host mating signal, they may also facilitate hybridization. Here we show how parasite-induced naris enlargement affects vocal quality, resulting in blurred species mating signals.
Tool use and social homophily among male bottlenose dolphins
Authors: Bizzozzero M. R. , Allen S. J. , Gerber L. , Wild S. , King S. L. , Connor R. C. , Friedman W. R. , Wittwer S. , Krützen M.
Published: June 2019

Homophilous behaviour plays a central role in the formation of human friendships. Individuals form social ties with others that show similar phenotypic traits, independently of relatedness. Evidence of such homophily can be found in bottlenose dolphins (Tursiops aduncus) in Shark Bay, Western Australia, where females that use marine sponges as foraging tools often associate with other females that use sponges. ‘Sponging’ is a socially learned, time-consuming behaviour, transmitted from mother to calf. Previous research illustrated a strong female bias in adopting this technique. The lower propensity for males to engage in sponging may be due to its incompatibility with adult male-specific behaviours, particularly the formation of multi-level alliances. However, the link between sponging and male behaviour has never been formally tested. Here, we show that male spongers associated significantly more often with other male spongers irrespective of their level of relatedness. Male spongers spent significantly more time foraging, and less time resting and travelling, than did male non-spongers. Interestingly, we found no difference in time spent socializing. Our study provides novel insights into the relationship between tool use and activity budgets of male dolphins, and indicates social homophily in the second-order alliance composition of tool-using bottlenose dolphins.
Comparing fitness and drift explanations of Neanderthal replacement
Authors: Shultz Daniel R. , Montrey Marcel , Shultz Thomas R.
Published: June 2019

There is a general consensus among archaeologists that replacement of Neanderthals by anatomically modern humans in Europe occurred around 40–35 ka. However, the causal mechanism for this replacement continues to be debated. Proposed models have featured either fitness advantages in favour of anatomically modern humans or invoked neutral drift under various preconditions. Searching for specific fitness advantages in the archaeological record has proven difficult, as these may be obscured, absent or subject to interpretation. To bridge this gap, we rigorously compare the system-level properties of fitness- and drift-based explanations of Neanderthal replacement. Our stochastic simulations and analytical predictions show that, although both fitness and drift can produce replacement, they present important differences in (i) required initial conditions, (ii) reliability, (iii) time to replacement, and (iv) path to replacement (population histories). These results present useful opportunities for comparison with archaeological and genetic data. We find greater agreement between the available empirical evidence and the system-level properties of replacement by differential fitness, rather than by neutral drift.
Soft Windowing Application to Improve Analysis of High-throughput Phenotyping Data
Authors: Haselimashhadi Hamed , Jeremy Mason C. , Munoz-Fuentes Violeta , López-Gómez Federico , Babalola Kolawole , Acar Elif F. , Kumar Vivek , White Jacqui , Flenniken Ann M. , King Ruairidh , Straiton Ewan , Seavitt John Richard , Gaspero Angelina , Garza Arturo , Christianson Audrey E. , Hsu Chih-Wei , Reynolds Corey L. , Lanza Denise G. , Lorenzo Isabel , Green Jennie R. , Gallegos Juan J. , Bohat Ritu , Samaco Rodney C. , Veeraragavan Surabi , Kim Jong Kyoung , Miller Gregor , Fuchs Helmut , Garrett Lillian , Becker Lore , Kang Yeon Kyung , Clary David , Cho Soo Young , Tamura Masaru , Tanaka Nobuhiko , Soo Kyung Dong , Bezginov Alexandr , About Ghina Bou , Champy Marie-France , Vasseur Laurent , Leblanc Sophie , Meziane Hamid , Selloum Mohammed , Reilly Patrick T. , Spielmann Nadine , Maier Holger , Gailus-Durner Valerie , Sorg Tania , Hiroshi Masuya , Yuichi Obata , Heaney Jason D. , Dickinson Mary E , Wolfgang Wurst , Tocchini-Valentini Glauco P. , Lloyd Kevin C. Kent , McKerlie Colin , Seong Je Kyung , Yann Herault , de Angelis Martin Hrabé , Brown Steve D.M. , Smedley Damian , Flicek Paul , Mallon Ann-Marie , Parkinson Helen , Meehan Terrence F.
Published: June 2019

Motivation

High-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximises analytic power while minimising noise from unspecified environmental factors.

Results

Here we introduce “soft windowing”, a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype-phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant p-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft windowed and non-windowed approaches, respectively, from a set of 2,082 mutant mouse lines. Our method is generalisable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources.

Availability and Implementation

The method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin.
Sex-specific prefrontal cortex dysfunction underlying opioid-induced cognitive impairment
Authors: Anderson Eden M. , Engelhardt Annabel , Demis Skyler , Porath Elissa , Hearing Matthew C.
Published: June 2019

Women transition to addiction faster and experience greater difficulties remaining abstinent; however, what drives this is unknown. Although poorly understood, loss of cognitive control following chronic drug use has been linked to decreased activation of frontal cortical regions. We show that self-administration of the opioid, remifentanil, causes a long-lasting decrease inex vivoexcitability but augments firing capacity of pyramidal neurons in the prelimbic cortex. This phenomenon occurs faster in females, manifests from sex-specific changes in excitatory and inhibitory synaptic regulation and aligns with impairments in cognitive flexibility. Further, chemogenetic induction of a hypoactive pyramidal neuron state in drug-naïve mice produces deficits, while compensating for this hypoactive state protects against cognitive inflexibility resulting from opioid self-administration. These data define cellular and synaptic mechanisms by which opioids impair prefrontal function and cognitive control and indicate that interventions aimed at treating opioid addiction must be tailored based on biological sex.
Influence of genetic interactions on polygenic prediction
Authors: Dai Zhijun , Long Nanye , Huang Wen
Published: June 2019

Prediction of phenotypes from genotypes is an important objective to fulfill the promises of genomics, precision medicine and agriculture. Although it’s now possible to account for the majority of genetic variation through model fitting, prediction of phenotypes remains a challenge, especially across populations that have diverged in the past. In this study, we designed simulation experiments to specifically investigate the role of genetic interactions in failure of polygenic prediction. We found that non-additive genetic interactions can significantly reduce the accuracy of polygenic prediction. Our study demonstrated the importance of considering genetic interactions in genetic prediction.
Networks of enhancers and microRNAs drive variation in cell states
Authors: Chakraborty Meenakshi , Hu Sofia , Del Giudice Marco , De Martino Andrea , Bosia Carla , Sharp Phillip A. , Garg Salil
Published: June 2019

Cell-to-cell variation in gene expression is a common feature of developmental processes. Yet, it remains unclear whether molecular mediators can generate variation and how this process is coordinated across loci to allow the emergence of new cell states. Using embryonic stem cells (ESCs) as a model of development, we found interconverting cell states that resemble developmental expression programs and vary in activity at specific enhancers, such as those regulating pluripotency genesNanogandSox2but notPou5f1(Oct4). Variable enhancers drive expression of variable genes, including those encoding microRNAs (miRNAs). Notably, variable miRNAs increase cell-to-cell variation by acting on neighborhoods of pluripotency genes. The encoded, variable pluripotency factors bind variable enhancers, forming a feedback loop that amplifies variation and allows the emergence of new cell states. These findings suggest gene regulatory networks composed of enhancers, protein-coding genes, and miRNAs harness inherent variation into developmental outcomes.
Diversity and disease: evidence for the monoculture effect beyond agricultural systems
Authors: Ekroth Alice K.E. , Rafaluk-Mohr Charlotte , King Kayla C.
Published: June 2019

Human activities are greatly reducing the genetic diversity of species worldwide. Given the prediction that parasites better exploit less diverse host populations, many species could be vulnerable to disease outbreaks. However, the widespread nature of the ‘monoculture effect’ remains unclear outside agricultural systems. We conducted a meta-analysis of 22 studies, obtaining a total of 66 effect sizes, to directly test the biological conditions under which host genetic diversity limits infectious disease in populations. Overall, we found broad support for the monoculture effect across host and parasite species. The effect was independent of host range, host reproduction, parasite diversity, and the method by which the monoculture effect was recorded. Conversely, we found that parasite functional group, virulence, and empirical environment matters. Together, these results highlight the general susceptibility of genetically homogenous populations to infection. Consequently, this phenomenon could become increasingly common and alarming for at-risk populations due to human-driven declines in genetic diversity and shifts in parasite distributions.
Neurophysiological Substrates of Configural Face Perception in Schizotypy
Authors: Ahn Sangtae , Lustenberger Caroline , Jarskog L. Fredrik , Fröhlich Flavio
Published: June 2019

Face perception is a highly developed function of the human visual system. Previous studies of event-related potentials (ERPs) have identified a face-selective ERP component (negative peak at about 170 milliseconds after stimulation onset, N170) in healthy participants. In contrast, patients with schizophrenia exhibit reduced amplitude of the N170, which may represent a pathological deficit in the neurophysiology of face perception. Interestingly, healthy humans with schizophrenia-like experiences (schizotypy) also exhibit abnormal processing of face perception. Yet, it has remained unknown how schizotypy in healthy humans is associated with the neurophysiological substrate of face perception. Here, we recruited 35 participants and assessed their schizotypy by the magical ideation rating scale. We used high-density electroencephalography to obtain ERPs elicited by a set of Mooney faces (face and non-face conditions). We divided the participants into two groups (high and low schizotypy) by a median split of schizotypy scores. We investigated mean reaction times and the N170 component in response to the stimuli. We found significant slowed reaction times and reduced amplitude of the N170 component in response to the face stimuli in the high-schizotypy group. In addition, across the full data set, we found that the schizotypy scores were significantly correlated with both the reaction times and the N170 amplitude. Our results thus support the model of schizotypy as a manifestation of a continuum between healthy individuals and patients with schizophrenia, where the N170 impairment serves as a biomarker for the degree of pathology along this continuum.
Tipping-point analysis uncovers critical transition signals from gene expression profiles
Authors: Yang Xinan H , Wang Zhezhen , Goldstein Andrew , Sun Yuxi , Rowton Megan , Wang Yanqiu , Griggs Dannie , Moskowitz Ivan , Cunningham John M
Published: June 2019

Differentiation involves bifurcations between discrete cell states, each defined by a distinct gene expression profile. Single-cell RNA profiling allows the detection of bifurcations. However, while current methods capture these events, they do not identify characteristic gene signals. Here we show that BioTIP – a tipping-point theory-based analysis – can accurately, robustly, and reliably identify critical transition signals (CTSs). A CTS is a small group of genes with high covariance in expression that mark the cells approaching a bifurcation. We validated its accuracy in the cardiogenesis with known a tipping point and demonstrated the identified CTSs contain verified differentiation-driving transcription factors. We then demonstrated the application on a published mouse gastrulation dataset, validated the predicted CTSs using independent in-vivo samples, and inferred the key developing mesoderm regulator Etv2. Taken together, BioTIP is broadly applicable for the characterization of the plasticity, heterogeneity, and rapid switches in developmental processes, particularly in single-cell data analysis.

Highlights

Identifying significant critical transition signals (CTSs) from expression noise

A significant CTS contains or is targeted by key transcription factors

BioTIP identifies CTSs accurately and independent of trajectory topologies

Significant CTSs reproducibly indicate bifurcations across datasets
Synchronization of mammalian motile cilia in the brain with hydrodynamic forces
Authors: Pellicciotta Nicola , Hamilton Evelyn , Kotar Jurij , Faucourt Marion , Degehyr Nathalie , Spassky Nathalie , Cicuta Pietro
Published: June 2019

Motile cilia are widespread across the animal and plant kingdoms, displaying complex collective dynamics central to their physiology. Their coordination mechanism is not generally understood, with pre-vious work mainly focusing on algae and protists. We study here the synchronization of cilia beat in multiciliated cells from brain ven-tricles. The response to controlled oscillatory external flows shows that strong flows at a similar frequency to the actively beating cilia can entrain cilia oscillations. We find that the hydrodynamic forces required for this entrainment strongly depend on the number of cilia per cell. Cells with few cilia (up to five) can be entrained at flows comparable to the cilia-driven flows reported in vivo. Simulations of a minimal model of cilia interacting hydrodynamically show the same trends observed in cilia. Our results suggest that hydrody-namic forces between cilia are sufficient to be the mechanism behind the synchronization of mammalian brain cilia dynamics.

Significance Statement

It is shown experimentally, and also reproducing key qualitative results in a minimal mechanistic model simulated numerically, that in the motile cilia of the brain hydrodynamic forces of the magnitude that cilia themselves can generate are sufficient to establish the coordination of dynamics which is so crucial phys-iologically. This is the first experiment of its kind on multicilated cells, the key result is the unexpected importance of cilia num-ber per cell, with cells with fewer cilia much more susceptible to external flows. This finding changes the way in which we think about the question of collective cilia beating - it is not correct to simply examine isolated cilia and draw conclusions about the behaviour of cilia assemblies in multiciliated cells.
β-blockers augment L-type Ca2+channel activity by target-selective spatially restricted β2AR-cAMP-PKA signaling in neurons
Authors: Shen Ao , Chen Dana , Kaur Manpreet , Xu Bing , Shi Qian , Martinez Joseph M. , Man Kwun-nok Mimi , Hell Johannes W. , Navedo Manuel F. , Yu Xi-Yong , Xiang Yang K.
Published: June 2019

G protein-coupled receptors (GPCRs) transduce pleiotropic intracellular signals in mammalian cells. Here, we report that some antagonists of β adrenergic receptors (βARs) such as β-blocker carvedilol and alprenolol activate β2AR at nanomolar concentrations, which promote G protein signaling and cAMP/PKA activity without action of G protein receptor kinases (GRKs). The cAMP/PKA signal is restricted within the local plasma membrane domain, leading to selectively enhance PKA-dependent augment of endogenous L-type calcium channel (LTCC) activity but not AMPA receptor in hippocampal neurons. Moreover, we have engineered a mutant β2AR that lacks serine 204 and 207 in the catecholamine binding pocket. This mutant can be preferentially activated by carvedilol but not the orthosteric agonist isoproterenol. Carvedilol activates the mutant β2AR in hippocampal neurons augmenting LTCC activity through cAMP/PKA signaling. Together, our study identifies a mechanism by which β-blocker-dependent activation of GPCRs at low ligand concentrations promotes local cAMP/PKA signaling to selectively target membrane downstream effectors such as LTCC in neurons.
The inter-dimeric interface controls function and stability ofUreaplasma urealiticummethionine S-adenosyltransferase
Authors: Kleiner Daniel , Shmulevich Fannia , Zarivach Raz , Shahar Anat , Sharon Michal , Ben-Nissan Gili , Bershtein Shimon
Published: June 2019

Methionine S-adenosyltransferases (MATs) are predominantly homotetramers, comprised of dimers of dimers. The highly conserved dimeric interface harbors two active sites, making the dimer the obligatory functional unit. Yet, functionality of the recently evolved inter-dimeric interface remains unknown. Here, we show that the inter-dimeric interface ofU. urealiticumMAT has evolved to control the catalytic activity and structural integrity of the homotetramer in response to product accumulation. When all four active sites are occupied with the product, S-adenosylmethionine (SAM), binding of four additional SAM molecules to the inter-dimeric interface prompts a ∼45° shift in the dimer orientation and a concomitant ∼60% increase in the interface area. This rearrangement inhibits the enzymatic activity by locking the flexible active site loops in a closed state and renders the tetramer resistant to proteolytic degradation. Our findings suggest that the inter-dimeric interfaces of MATs are recruited by evolution to tune the molecular properties of the entire homotetramer.
BAMscale: quantification of DNA sequencing peaks and generation of scaled coverage tracks
Authors: Pongor Lorinc S. , Gross Jacob M. , Alvarez Roberto Vera , Murai Junko , Jang Sang-Min , Zhang Hongliang , Redon Christophe , Fu Haiqing , Huang Shar-Yin , Thakur Bhushan , Baris Adrian , Marino-Ramirez Leonardo , Landsman David , Aladjem Mirit I. , Pommier Yves
Published: June 2019

BAMscale is a one-step tool that processes DNA sequencing datasets from chromatin binding (ChIP-seq) and chromatin state changes (ATAC-seq, END-seq) experiments to DNA replication data (OK-seq, NS-seq and replication timing). The outputs include normalized peak scores in text format and scaled coverage tracks (BigWig) which are directly accessible to data visualization programs. BAMscale (available at https://github.com/ncbi/BAMscale) effectively processes large sequencing datasets (~100Gb size) in minutes, outperforming currently available tools.
A Synthetic Peptide Encoded by a Random DNA Sequence Inhibits Discrete Red Light Responses
Authors: Shuipys Tautvydas , Carvalho Raquel F. , Clancy Maureen A. , Bao Zhilong , Folta Kevin M.
Published: June 2019

We have identified a synthetic peptide that interrupts discrete aspects of seedling development under red light. Previous reports have demonstrated that plants transformed with random DNA sequences produce synthetic peptides that affect plant biology. In this report one specific peptide is characterized that inhibits discrete aspects of red-light-mediated Arabidopsis thaliana development during photomorphogenesis. Seedlings expressing the PEP6-32 peptide presented longer hypocotyls and diminished cotyledon expansion when grown under red light. Other red-light-mediated seedling processes such as induction of Lhcb (cab) transcripts or loss of vertical growth remained unaffected. Long-term responses to red light in PEP6-32 expressing plants, such as repression of flowering time, did not show defects in red light signaling or integration. A synthesized peptide applied exogenously induced the long-hypocotyl phenotype under red light in non-transformed seedlings. The results indicate that the PEP6-32 peptide causes discrete cell expansion defects during early seedling development in red light, mimicking weak phyB alleles in some aspects of seedling photomorphogenesis. The findings demonstrate that new chemistries derived from random peptide expression can modulate specific facets of plant growth and development.

One Sentence Summary

A plant line expressing random DNA sequence expresses a synthetic peptide that affects specific red-light responses in a developing seedling.
Stimulation augments spike sequence replay and memory consolidation during slow-wave sleep
Authors: Wei Yina , Krishnan Giri P , Marshall Lisa , Martinetz Thomas , Bazhenov Maxim
Published: June 2019

Newly acquired memory traces are spontaneously reactivated during slow-wave sleep (SWS), leading to the consolidation of recent memories. Empirical studies found that sensory stimulation during SWS selectively enhances memory consolidation and the effect depends on the phase of stimulation. In this new study, we aimed to understand the mechanisms behind the role of sensory stimulation on memory consolidation using computational models implementing effects of neuromodulators to simulate transitions between awake and SWS sleep, and synaptic plasticity to allow the change of synaptic connections due to the training in awake or replay during sleep. We found that when closed-loop stimulation was applied during the Down states (900-2700) of sleep slow oscillation, particularly right before transition from Down to Up state, it significantly affected the spatio-temporal pattern of the slow-waves and maximized memory replay. In contrast, when the stimulation was presented during the Up states (2700-3600 and 00-900), it did not have a significant impact on the slow-waves or memory performance after sleep. For multiple memories trained in awake, presenting stimulation cues associated with specific memory trace could selectively augment replay and enhance consolidation of that memory and interfere with consolidation of the others (particularly weak) memories. Our study proposes a synaptic level mechanism of how memory consolidation is affected by sensory stimulation during sleep.

Significance statement

Stimulation, such as training-associated cues or auditory stimulation, during sleep can augment consolidation of the newly encoded memories. In this study, we used a computational model of the thalamocortical system to describe the mechanisms behind the role of stimulation in memory consolidation during slow-wave sleep. Our study suggested that stimulation preferentially strengthens the memory traces when delivered at specific phase of slow oscillations just before Down to Up state transition when it makes the largest impact on the spatio-temporal pattern of sleep slow waves. In the presence of multiple memories, presenting sensory cues during sleep could selectively strengthen selected memories. Our study proposes a synaptic level mechanism of how memory consolidation is affected by sensory stimulation during sleep.
Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets
Authors: Srivastava Shivani , Pandey Harsh , Singh Surya Kumar , Tripathi Yamini Bhusan
Published: June 2019

Background and Aim

Earlier assessment of Pueraria tuberosa tubers has shown anti-diabetic effects through incretin mimetic action and DPP-IV inhibition. The aim of this work was to further explore the protective role of aqueous extract of Pueraria tuberosa against streptozotocin (STZ)-induced pancreatic stress in rats.

Methods

Diabetes was induced with STZ (65 mg/kg body weight) in Charles foster male rats. After 60 days of STZ administration, animals with blood glucose levels > 200 g/dL were considered as diabetic. All the rats were later divided into three groups: Group-1 (STZ untreated normal rats), Group-2 (Diabetic control), and Group-3 (PTY-2 [50 mg/100 g bw treatment for next 10 days to diabetic rats). The rats were then sacrificed at the 10th day of treatment accordingly.

Results

STZ treatment led to an increase in expression of MMP-9, Tnf α, HIF-1α, VEGF, IL-6, PKC ε, NF-kB, and Caspase-3. Reverse transcriptase Polymerase Chain Reaction (PCR), IHC and western blot analysis showed an increase in the expressions of superoxide dismutase (SOD) and Nephrin, and a decrease in the expressions of NF-kB, PKC ε, TNF-α MMP-9, HIF-1α, VEGF, Caspase 3 and IL-6 after 10 days of PTY-2 treatment.

Conclusion

The results show that PTY-2 favorably changed the expression of NF-kB, PKC ε, TNF α, MMP 9, HIF-1α, VEGF, IL-6, Caspase3, Nephrin and SOD in cases of STZ-induced pancreatic stress. Further evaluation of PTY-2 might be helpful in establishing its role in the management of diabetes mellitus.

Highlights

PTY 2 act as a protective herbal drug against STZ induced islet stress.

PTY 2 upregulates protective and downregulates harmful markers.

This study composed of four pathway through which PTY 2 acts on pancreas.

GRAPHICAL ABSTRACT

Mechanism of action of PTY 2 against STZ induced islet stress.
Efficient depletion of ribosomal RNA for RNA sequencing in planarians
Authors: Kim Iana V. , Ross Eric J. , Dietrich Sascha , Döring Kristina , Sánchez Alvarado Alejandro , Kuhn Claus-D.
Published: June 2019

Background

The astounding regenerative abilities of planarian flatworms prompt a steadily growing interest in examining their molecular foundation. Planarian regeneration was found to require hundreds of genes and is hence a complex process. Thus, RNA interference followed by transcriptome-wide gene expression analysis by RNA-seq is a popular technique to study the impact of any particular planarian gene on regeneration. Typically, the removal of ribosomal RNA (rRNA) is the first step of all RNA-Seq library preparation protocols. To date, rRNA removal in planarians was primarily achieved by the enrichment of polyadenylated (poly(A)) transcripts. However, to better reflect transcriptome dynamics and to cover also non-poly(A) transcripts, a procedure for the targeted removal of rRNA in planarians is needed.

Results

In this study, we describe a workflow for the efficient depletion of rRNA in the planarian model species S. mediterranea. Our protocol is based on subtractive hybridization using organism-specific probes. Importantly, the designed probes also deplete rRNA of other freshwater triclad families, a fact that considerably broadens the applicability of our protocol. We tested our approach on total RNA isolated stem cells (termed neoblasts) of S. mediterranea and compared ribodepleted libraries with publicly available poly(A)-enriched ones. Overall, mRNA levels after ribodepletion were consisted with poly(A) libraries. However, ribodepleted libraries revealed higher transcript levels for transposable elements and histone mRNAs that remained underrepresented in poly(A) libraries. As neoblasts experience high transposon activity this suggests that ribodepleted libraries better reflect the transcriptional dynamics of planarian stem cells. Furthermore, the presented ribodepletion procedure was successfully expanded to the removal of ribosomal RNA from the gram-negative bacterium Salmonella typhimurium.

Conclusions

The ribodepletion protocol presented here ensures the efficient rRNA removal from low input total planarian RNA, which can be further processed for RNA-Seq applications. Resulting libraries contain less than 2% rRNA. Moreover, for a cost-effective and efficient removal of rRNA prior to sequencing applications our procedure might be adapted to any prokaryotic or eukaryotic species of choice.
Nucleotide-mediated allosteric regulation of bifunctional Rel enzymes
Authors: Tamman Hedvig , Van Nerom Katleen , Takada Hiraku , Vandenberk Niels , Scholl Daniel , Polikanov Yury , Hofkens Johan , Talavera Ariel , Hauryliuk Vasili , Hendrix Jelle , Garcia-Pino Abel
Published: June 2019

Bifunctional Rel stringent factors, the most broadly distributed class of RSHs, are ribosome-associated enzymes that transfer a pyrophosphate group from ATP onto the 3′ of GTP or GDP to synthesize (p)ppGpp and also catalyse the 3′ pyrophosphate hydrolysis of the alarmone to degrade it. The precise regulation of these enzymes seems to be a complex allosteric mechanism, and despite decades of research, it is unclear how the two opposing activities of Rel are controlled at the molecular level. Here we show that a stretch/recoil guanosine-switch mechanism controls the catalytic cycle of T. thermophilus Rel (RelTf). The binding of GDP/ATP stretches apart the NTD catalytic domains of RelTf (RelTtNTD) activating the synthetase domain and allosterically blocking the hydrolase active site. Conversely, binding of ppGpp unlocks the hydrolase domain and triggers recoil of both NTDs, which partially buries the synthetase active site and precludes the binding of synthesis precursors. This allosteric mechanism acts as an activity switch preventing futile cycles of alarmone synthesis and degradation.
Antibiotic resistant bacteria and commensal fungi are common and conserved in the mosquito microbiome
Authors: Hyde Josephine , Gorham Courtney , Brackney Doug E. , Steven Blaire
Published: June 2019

The emerging and increasing prevalence of bacterial antibiotic resistance is a significant public health challenge. To begin to tackle this problem, it will be critical to not only understand the origins of this resistance but also document environmental reservoirs of antibiotic resistance. In this study we investigated the possibility that both colony and field caught mosquitoes could harbor antibiotic resistant bacteria. Specifically, we characterized the antibiotic resistant bacterial populations from colony-reared Aedes aegypti larvae and adults and two field caught mosquito species Coquillettidia perturbans and Ochlerotatus canadensis. The cultured bacterial populations were dominated by isolates belonging to the class Gammaproteobacteria. Among the antibiotic resistant populations, we found bacteria resistant to carbenicillin, kanamycin, and tetracycline, including bacteria resistant to a cocktail of all three antibiotics in combination. The antibiotic resistant bacteria were numerically rare, at most 5% of total cell counts. Isolates were characterized by 16S rRNA gene sequencing, and clustering into Operational Taxonomic Units (OTUs; 99% sequence identity). 27 antibiotic resistant OTUs were identified, although members of an OTU did not always share the same resistance profile. This suggests the clustering was either not sensitive enough to distinguish different bacteria taxa or different antibiotic resistant sub-populations exist within an OTU. Finally, the antibiotic selection opened up a niche to culture mosquito-associated fungi, and 10 fungal OTUs (28S rRNA gene sequencing) were identified. Two fungal OTUs both classified to the class Microbotryomycetes were commonly identified in the field-caught mosquitoes. Thus, in this study we demonstrate that antibiotic resistant bacteria and certain fungi are common and conserved mosquito microbiome members. These observations highlight the potential of invertebrates to serve as vehicles for the spread of antibiotic resistance throughout the environment.
Mechanization services, farm productivity and institutional innovation in China
Authors: Qing Yi , Chen Moyu , Sheng Yu , Huang Jikun
Published: June 2019

Purpose

The purpose of this paper is to investigate the impact of mechanization services on farm productivity in Northern China from an empirical perspective, with the aim to identify the underlying market and institutional barriers.

Design/methodology/approach

The authors apply the regression method with the control of village fixed effects to examining the relationship between capital–labor ratio, mechanization service ratio and farm productivity, using the panel data collected in 2013 and 2015 by CCAP.

Findings

Mechanization services improve farm productivity through substituting labor, but it may generate a less positive impact on farms who do not have self-owned capital equipment.

Originality/value

It is the first study to investigate how mechanization services affect farm productivity for grain producers in Northern China.
Natural convection in differentially heated enclosures subjected to variable temperature boundaries
Authors: Mohamad Abdulmajeed , Sheremet Mikhail A. , Taler Jan , Ocłoń Paweł
Published: June 2019

Purpose

Natural convection in differentially heated enclosures has been extensively investigated due to its importance in many industrial applications and has been used as a benchmark solution for testing numerical schemes. However, most of the published works considered uniform heating and cooling of the vertical boundaries. This paper aims to examine non-uniform heating and cooling of the mentioned boundaries. The mentioned case is very common in many electronic cooling devices, thermal storage systems, energy managements in buildings, material processing, etc.

Design/methodology/approach

Four cases are considered, the left-hand wall’s temperature linearly decreases along the wall, while the right-hand wall’s temperature is kept at a constant, cold temperature. In the second case, the left-hand wall’s temperature linearly increases along the wall, while the right-hand wall’s temperature is kept a constant, cold temperature. The third case, the left-hand wall’s temperature linearly decreases along the wall, while the right-hand wall’s temperature linearly increases along the wall. In the fourth case, the left-hand and the right-hand walls’ temperatures decrease along the wall, symmetry condition. Hence, four scenarios of natural convection in enclosures were covered.

Findings

It has been found that the average Nusselt number of the mentioned cases is less than the average Nusselt number of the uniformly heated and cooled enclosure, which reflects the physics of the problem. The work quantifies the deficiency in the rate of the heat transfer. Interestingly one of the mentioned cases showed two counter-rotating horizontal circulations. Such a flow structure can be considered for passively, highly controlled mechanism for species mixing processes application.

Originality/value

Previous works assumed that the vertical boundary is subjected to a constant temperature or to a sinusoidal varying temperature. The subject of the work is to examine the effect of non-uniformly heating and/or cooling vertical boundaries on the rate of heat transfer and flow structure for natural convection in a square enclosure. The temperature either linearly increases or decreases along the vertical coordinate at the boundary. Four scenarios are explored.
Capital market development and bank efficiency: a cross-country analysis
Authors: Ngo Thanh , Le Tu
Published: June 2019

Purpose

The purpose of this paper is to empirically investigate the causal relationship between banking efficiency and capital market development in 86 countries between 2006 and 2011.

Design/methodology/approach

The authors follow the two-stage framework: data envelopment analysis (DEA) with the use of financial ratios is used to arrive at efficiency scores of the banks in the first stage. Thereafter, those efficiency scores will be linked with the development level of the capital markets of the corresponding country in the second stage using the generalised method of moments in a simultaneous equations model.

Findings

The authors found that banking systems around the world were still inefficient, suggesting that it would take time for the global banking system to recover after the global financial crisis 2007/2008. More importantly, the findings demonstrated that the larger the capital market is, the less efficient its banking system would be. In contrast, banking efficiency can positively influence the development of the capital market.

Research limitations/implications

The data are unbalanced and limited to 86 countries; the study did not analyse the productivity change over time of those banking systems; and it would be useful to test the first-stage DEA with different sets of variables as well as different assumptions.

Practical implications

The paper suggests that for any economy around the world, an improvement in banking performance and efficiency rather than capital market development should be a priority, alongside with monitoring inflation.

Originality/value

The paper provides an unbiased analysis of the causal relationship between the banking sector and the capital market.