bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrethroids inhibit K2P channels and activate sensory neurons: basis of insecticide-induced paraesthesias
Authors: Castellanos Aida , Andres Alba , Bernal Laura , Callejo Gerard , Comes Nuria , Gual Arcadi , Giblin Jonathan P. , Roza Carolina , Gasull Xavier
Published: September 2017

Pyrethroid insecticides are widely used for pest control in agriculture or in human public health commonly as a topical treatment for scabies and head lice. Exposure to pyrethroids such as permethrin or tetramethrin (TM) causes sensory alterations such as transient pain, burning, stinging sensations, and paraesthesias. Despite the well-known effects of pyrethroids on sodium channels, actions on other channels that control sensory neuron excitability are less studied. Given the role of 2-pore domain potassium (K2P) channels in modulating sensory neuron excitability and firing, both in physiological and pathological conditions, we examined the effect of pyrethroids on K2P channels mainly expressed in sensory neurons. Through electrophysiological and calcium imaging experiments, we show that a high percentage of TM-responding neurons were nociceptors, which were also activated by TRPA1 and/or TRPV1 agonists. This pyrethroid also activated and enhanced the excitability of peripheral saphenous nerve fibers. Pyrethroids produced a significant inhibition of native TRESK, TRAAK, TREK-1, and TREK-2 currents. Similar effects were found in transfected HEK293 cells. At the behavioral level, intradermal TM injection in the mouse paw produced nocifensive responses and caused mechanical allodynia, demonstrating that the effects seen on nociceptors in culture lead to pain-associated behaviors in vivo. In TRESK knockout mice, pain-associated behaviors elicited by TM were enhanced, providing further evidence for a role of this channel in preventing excessive neuronal activation. Our results indicate that inhibition of K2P channels facilitates sensory neuron activation and increases their excitability. These effects contribute to the generation of paraesthesias and pain after pyrethroid exposure.
Implications of GLAGOV study
Authors: Nicholls Stephen J. , Puri Rishi
Published: September 2017

Purpose of review

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition has emerged as a novel approach to lowering levels of low-density lipoprotein cholesterol (LDL-C). The impact of PCSK9 inhibition in statin-treated patients on coronary atherosclerosis had remained unknown.

Recent findings

The GLAGOV trial compared the effect of the PCSK9 inhibitor, evolocumab, and placebo on progression of coronary atherosclerosis in patients treated with at least moderate intensity statin therapy. Predictable lowering of LDL-C with evolocumab (36.6 versus 93.0 mg/dl) associated with significant regression of coronary atherosclerosis. A direct relationship was observed between achieved LDL-C levels and disease progression.

Addition of evolocumab to statin therapy produces incremental regression of plaque regression in patients with established coronary artery disease. This finding provides a biological rationale for the reported beneficial effects of evolocumab on cardiovascular events.
Presence of Human Herpesvirus 6B in the Pancreas of Subjects With and Without Type 1 Diabetes
Authors: Ericsson Maja , Skog Oskar
Published: September 2017

Objectives

The aims of this study were to investigate the presence of human herpesvirus 6 (HHV6) A and B in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (T1D).

Methods

Pancreata from brain-dead organ donors with and without T1D were examined for the presence of HHV6 genomic sequences by polymerase chain reaction (PCR), transcripts by reverse transcriptase–PCR, and protein by immunohistochemistry. Quantitative PCR of isolated pancreatic islets and exocrine cell clusters was used to determine the intrapancreatic location of HHV6 DNA.

Results

Human herpesvirus 6B genomic sequences were present in 1 of 2 donors who died of acute-onset T1D, 4 of 6 donors with long-standing T1D, and 9 of 12 nondiabetic donors. Higher copy numbers of HHV6B DNA were present in isolated islets than in exocrine tissue from the same donors. No signs of active HHV6 transcription were found. Human herpesvirus 6A was not present in any tested pancreas.

Conclusions

The herein presented data demonstrate, for the first time, the presence of a latent HHV6B infection in the pancreas and islets of Langerhans. Whether this virus can contribute to disease in the pancreas remains to be determined.
The Etiology of Male Urethral Discharge in Zimbabwe: Results from the Zimbabwe STI Etiology Study
Authors: Rietmeijer Cornelis A. , Mungati More , Machiha Anna , Mugurungi Owen , Kupara Vitalis , Rodgers Luanne , Kilmarx Peter H. , Roloff Amy Herman , Gonese Elizabeth , Tippett-Barr Beth A. , Shambira Gerald , Lewis David A. , Handsfield H. Hunter , Tshimanga Mufuta
Published: September 2017

Introduction

Sexually transmitted infections (STIs) are managed syndromically in most developing countries. In Zimbabwe, men presenting with urethral discharge are treated with a single intramuscular dose of kanamycin or ceftriaxone in combination with a week’s course of oral doxycycline. This study was designed to assess the current etiology of urethral discharge and other STIs to inform current syndromic management regimens.

Methods

We conducted a study among 200 men with urethral discharge presenting at 6 regionally diverse STI clinics in Zimbabwe. Urethral specimens were tested by multiplex polymerase chain reaction testing for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis. In addition, serologic testing for syphilis and HIV was performed.

Results

Among the 200 studied men, one or more pathogens were identified in 163 (81.5%) men, including N. gonorrhoeae in 147 (73.5%), C. trachomatis in 45 (22.5%), T. vaginalis in 8 (4.0%), and M. genitalium in 7 (3.5%). Among all men, 121 (60%) had a single infection, 40 (20%) had dual infections, and 2 (1%) had 3 infections. Among the 45 men with C. trachomatis, 36 (80%) were coinfected with N. gonorrhoeae. Overall, 156 (78%) men had either N. gonorrhoeae or C. trachomatis identified. Of 151 men who consented to HIV testing, 43 (28.5%) tested positive. There were no differences in HIV status by study site or by urethral pathogen detected.

Conclusions

Among men presenting at Zimbabwe STI clinics with urethral discharge, N. gonorrhoeae and C. trachomatis are the most commonly associated pathogens. Current syndromic management guidelines seem to be adequate for the treatment for symptomatic men, but future guidelines must be informed by ongoing monitoring of gonococcal resistance.
The Significance of Arachnoid Granulation in Patients With Idiopathic Intracranial Hypertension
Authors: Watane Gaurav Vishwasrao , Patel Bhumi , Brown Derek , Taheri M. Reza
Published: September 2017

Purpose

The aim of this article was to study the significance of arachnoid granulations (AGs) in patients with idiopathic intracranial hypertension (IIH).

Methods

In an institutional review board–approved retrospective chart review study, 79 patients with clinical diagnosis of idiopathic increased intracranial pressure were compared with 63 patients with a diagnosis of multiple sclerosis. Inclusion criteria also included available magnetic resonance imaging (MRI) of the brain, older than 18 years, and female sex. Patients with elevated intracranial pressure due to other causes were excluded. The electronic medical records were mined for presence of the following: body mass index, age, headache, vision changes, tinnitus, and vertigo. The MRI of the brain was reviewed for the presence of the following features: empty sella, prominent cerebrospinal fluid space in the optic sheaths, tortuosity of the optic nerves and enlarged Meckel cave. In addition, the number, size, and location of AGs associated with major venous drainage sinuses were documented in all patients. Using statistical analysis, association between various imaging and clinical signs were evaluated.

Results

The association between AG and various imaging and clinical signs were evaluated. The percentage of patients with AG were significantly higher in patients with IIH. Patients with IIH tended to have 0 to 3 AG. The most common imaging findings observed in MRI of the brain of patients with IIH were empty sella and prominent cerebrospinal fluid space in the optic sheaths. The prevalence of these MRI findings in patients with IIH was inversely proportional to the number of AG. A similar inverse trend was also noted with the opening pressure of patients with IIH and number of AG.

Conclusions

The study establishes that there is a relationship between presence of AG and IIH. Arachnoid granulation seems to act in a compensatory mechanism in patients with IIH.
Iterative Metallic Artifact Reduction for In-Plane Gonadal Shielding During Computed Tomographic Venography of Young Males
Authors: Choi Jin Woo , Lee Sang Yub , Kim Jong Hyo , Jin Hyeongmin , Lee Jaewon , Choi Young Hun , Lee Hyeon-Kyeong , Park Jae Hyung
Published: September 2017

Objective

The purpose of this study was to evaluate a gonadal shield (GS) and iterative metallic artifact reduction (IMAR) during computed tomography scans, regarding the image quality and radiation dose.

Methods

A phantom was imaged with and without a GS. Prospectively enrolled, young male patients underwent lower extremity computed tomography venography (precontrast imaging without the GS and postcontrast imaging with the GS). Radiation dose was measured each time, and the GS-applied images were reconstructed by weighted filtered back projection and IMAR.

Results

In the phantom study, image artifacts were significantly reduced by using IMAR (P = 0.031), whereas the GS reduced the radiation dose by 61.3%. In the clinical study (n = 29), IMAR mitigated artifacts from the GS, thus 96.6% of the IMAR image sets were clinically usable. Gonadal shielding reduced the radiation dose to the testes by 69.0%.

Conclusions

The GS in conjunction with IMAR significantly reduced the radiation dose to the testes while maintaining the image quality.
Magnetic Resonance Imaging of the Soft Tissue Vascular Anomalies in Torso and Extremities in Children: An Update With 2014 International Society for the Study of Vascular Anomalies Classification
Authors: Snyder Elizabeth , Puttgen Kate , Mitchell Sally , Ahlawat Shivani , Tekes Aylin
Published: September 2017

Vascular anomalies can occur anywhere in the body, and the majority present in the pediatric population. Accurate classification is essential for proper clinical evaluation, particularly because multidisciplinary care is often required. The International Society for the Study of Vascular Anomalies classification offers a comprehensive classification for all subspecialties. In this review article, we present a magnetic resonance imaging protocol with exemplary cases of the most common types of vascular anomalies in the pediatric trunk and extremities using the current International Society for the Study of Vascular Anomalies classification.
Improved Calcium Scoring at Dual-Energy Computed Tomography Angiography Using a High-Z Contrast Element and Novel Material Separation Technique
Authors: Lambert Jack W. , Sun Yuxin , Ordovas Karen G. , Gould Robert G. , Wang Sizhe , Yeh Benjamin M.
Published: September 2017

Objectives

The aim of this study was to compare the accuracy of existing dual-energy computed tomography (CT) angiography coronary artery calcium scoring methods to those obtained using an experimental tungsten-based contrast material and a recently described contrast material extraction process (CMEP).

Methods

Phantom coronary arteries of varied diameters, with different densities and arcs of simulated calcified plaque, were sequentially filled with water, iodine, and tungsten contrast materials and scanned within a thorax phantom at rapid-kVp-switching dual-energy CT. Calcium and contrast density images were obtained by material decomposition (MD) and CMEP. Relative calcium scoring errors among the 4 reconstructed datasets were compared with a ground truth, 120-kVp dataset.

Results

Compared with the 120-kVp dataset, tungsten CMEP showed a significantly lower mean absolute error in calcium score (6.2%, P < 0.001) than iodine CMEP, tungsten MD, and iodine MD (9.9%, 15.7%, and 40.8%, respectively).

Conclusions

Novel contrast elements and material separation techniques offer improved coronary artery calcium scoring accuracy and show potential to improve the use of dual-energy CT angiography in a clinical setting.
Patient Burden of Axial Spondyloarthritis
Authors: Strand Vibeke , Singh Jasvinder A.
Published: September 2017

Axial spondyloarthritis (AxSpA) is an inflammatory spondyloarthritis (SpA) that has significant impact on a patient's life. Symptoms, including fatigue, sleep problems, depression, and sexual dysfunction, can profoundly impact health-related quality of life (HRQoL) and limit work, leisure, and daily activities. Available therapies effectively manage pain and inflammation in early-stage disease, but patients often continue to experience impaired HRQoL. Thus, there remains a need for new therapies with novel mechanisms that can stop disease progression, potentially reverse damage caused by AxSpA and improve HRQoL in patients with AxSpA. Newer biologic agents, such as those targeting the interleukin 17–interleukin 23 axis, have promising efficacy and may improve HRQoL for patients with AxSpA. The AxSpA has many negative effects on HRQoL. By targeting disease pathways responsible for the development of AxSpA, approved and emerging therapies potentially reduce disease activity and improve the functional status of patients with AxSpA. This narrative review reflects on the findings of studies evaluating HRQoL of individuals with AxSpA and the role of newer therapies.
Conical Modification of Forearm Free Flaps for Single-Stage Reconstruction After Total Orbital Exenteration
Authors: Purnell Chad A. , Vaca Elbert E. , Ellis Marco F.
Published: September 2017

Background:

Orbital exenteration is a significant reconstructive challenge for plastic surgeons. Options described for these defects range from healing by secondary intention to free tissue transfer. The authors present our preferred reconstruction of orbital defects with free forearm-based flaps, which provides quality soft tissue and orbital contouring in 1 stage to consistently allow placement of bone-anchored implants for eventual orbital prosthesis.

Methods:

This conical shape of the orbit is deconstructed into a “Pac-Man” type shaped flap that leaves adequate depth for a prosthesis. A retrospective chart review was performed of 2 separate patients receiving orbital exenteration reconstruction by the senior author (MFE).

Results:

Two patients presented with adenoid cystic carcinoma of the orbit. Both patients underwent nonlid sparing orbital exenteration with adjuvant chemotherapy and radiation. Each patient subsequently developed delayed wound healing after prior local flap reconstruction. Vascularized radial forearm flaps in a Pac-Man shape were used in both patients. Both patients were discharged from the hospital on postoperative day 3. No partial or total flap loss was encountered. To date, each patient has undergone planning for osseointegrated implants.

Conclusion:

The authors present a simplified method of orbital reconstruction that provides high-quality vascularized tissue for resurfacing in 1 stage. This type of open-cavity flap reconstruction avoids the need for flap debulking procedures and facilitates 2-stage placement of osseointegrated implants.
Thoracic irrigation prevents retained hemothorax: A prospective propensity scored analysis
Authors: Kugler Nathan W. , Carver Thomas W. , Milia David , Paul Jasmeet S.
Published: September 2017

BACKGROUND

Thoracic trauma resulting in hemothorax (HTx) is typically managed with thoracostomy tube (TT) placement; however, up to 20% of patients develop retained HTx which may necessitate further intervention for definitive management. Although optimal management of retained HTx has been extensively researched, little is known about prevention of this complication. We hypothesized that thoracic irrigation at the time of TT placement would significantly decrease the rate of retained HTx necessitating secondary intervention.

METHODS

A prospective, comparative study of patients with traumatic HTx who underwent bedside TT placement was conducted. The control group consisted of patients who underwent standard TT placement, whereas the irrigation group underwent standard TT placement with immediate irrigation using 1 L of warmed sterile 0.9% saline. Patients who underwent emergency thoracotomy, those with TTs removed within 24 hours, or those who died within 30 days of discharge were excluded. The primary end point was secondary intervention defined by additional TT placement or operative management for retained HTx. A propensity-matched analysis was performed with scores estimated using a logistic regression model based on age, sex, mechanism of injury, Abbreviated Injury Scale chest score, and TT size.

RESULTS

In over a 30-month period, a total of 296 patients underwent TT placement for the management of traumatic HTx. Patients were predominantly male (79.6%) at a median age of 40 years and were evenly split between blunt (48.8%) and penetrating (51.2%) mechanisms. Sixty (20%) patients underwent thoracic irrigation at time of initial TT placement. The secondary intervention rate was significantly lower within the study group (5.6% vs. 21.8%; OR, 0.16; p < 0.001). No significant differences in TT duration, ventilator days, or length of stay were noted between the irrigation and control cohort.

CONCLUSION

Thoracic irrigation at the time of initial TT placement for traumatic HTx significantly reduced the need for secondary intervention for retained HTx.

LEVEL OF EVIDENCE

Therapeutic Study, Level III.
Electroconvulsive Therapy for Super Refractory Status Epilepticus
Authors: Ahmed Jayme , Metrick Michael , Gilbert Anne , Glasson Anita , Singh Ranjeet , Ambrous Wayne , Brown Lori , Aykroyd Laura , Bobel Karen
Published: September 2017

Objectives

Super refractory status epilepticus (SRSE) is a stage beyond refractory status that requires general anesthesia as management. Electroconvulsive therapy (ECT) is recommended only as a potential treatment option beyond general anesthesia and after all other options have been exhausted. Its effect on aborting status has been minimally researched. We present the largest case series to our knowledge exploring the effect of ECT on SRSE.

Methods

Eight adults hospitalized for SRSE received ECT in an attempt to abort status after other treatment modalities were exhausted. Electroconvulsive therapy consisted of a 504-mC (≈99.4 J) stimulus delivered bifrontotemporally with a constant 0.5-millisecond pulse width. Seizure activity during ECT was monitored visually and correlated to the single-channel recording provided by the apparatus.

Results

There was neurotelemetry or clinical evidence of improvement within 24 hours after the full course of ECT treatment in 5 (63%) of the 8 cases. Cases that improved were given an average of 7.8 total ECT stimulations, eliciting an average of 4.2 total seizures.

Conclusions

Although it is difficult to determine the exact role of ECT in the improvement of 63% of our cases, we present a series of patients for whom pharmacotherapy, ketogenic diet, and general anesthesia otherwise did not produce an appreciable effect on status prior to implementation of ECT. These findings suggest that cases of SRSE may benefit from ECT administration.
A Randomized, Nonblind, Naturalistic Comparison of Efficacy and Cognitive Outcomes With Right Unilateral, Bifrontal, and Bitemporal Electroconvulsive Therapy in Schizophrenia
Authors: Bansod Aniket , Sonavane Sushma S. , Shah Nilesh B. , De Sousa Avinash A. , Andrade Chittaranjan
Published: September 2017

Background

There is little literature on the relative efficacy and cognitive safety of right unilateral (RUL), bifrontal (BF), and bitemporal (BT) electroconvulsive therapy (ECT) in schizophrenia.

Methods

We present a randomized, nonblind, naturalist comparison of a fixed course of 8 moderately high-dose RUL (n = 24), threshold BF (n = 27), and threshold BT (n = 31) ECT in patients with schizophrenia. Assessments included the Positive and Negative Syndrome Scale (PANSS), the Wechsler Memory Scale—Revised, and an autobiographical memory interview. A completer analysis was planned and conducted to capture the cognitive outcomes.

Results

The sample as a whole improved significantly on all efficacy outcomes and deteriorated significantly on all cognitive outcomes. The primary efficacy outcome, improvement in PANSS total scores, did not differ significantly across groups. The PANSS positive score (but no other subscale score) improved significantly less with RUL relative to BF and BT ECT. For autobiographical memory and for almost all Wechsler Memory Scale subtests, including memory quotient (the primary adverse effect outcome), BT ECT was associated with greater impairment than RUL or BF ECT. Importantly, all statistically significant differences between treatments were clinically small in magnitude.

Conclusions

In patients with schizophrenia who receive a fixed course of 8 ECTs, threshold BT ECT is associated with greater cognitive impairment across a range of measures, and moderately high-dose RUL ECT is associated with poorer efficacy against positive symptoms. Threshold BF ECT exhibits the best efficacy-cum-neurocognitive safety profile. All differences between groups, however, are small and perhaps clinically insignificant.
Colour and luminance contrasts predict the human detection of natural stimuli in complex visual environments
Authors: White Thomas E. , Rojas Bibiana , Mappes Johanna , Rautiala Petri , Kemp Darrell J.
Published: September 2017

Much of what we know about human colour perception has come from psychophysical studies conducted in tightly-controlled laboratory settings. An enduring challenge, however, lies in extrapolating this knowledge to the noisy conditions that characterize our actual visual experience. Here we combine statistical models of visual perception with empirical data to explore how chromatic (hue/saturation) and achromatic (luminant) information underpins the detection and classification of stimuli in a complex forest environment. The data best support a simple linear model of stimulus detection as an additive function of both luminance and saturation contrast. The strength of each predictor is modest yet consistent across gross variation in viewing conditions, which accords with expectation based upon general primate psychophysics. Our findings implicate simple visual cues in the guidance of perception amidst natural noise, and highlight the potential for informing human vision via a fusion between psychophysical modelling and real-world behaviour.
Paternal arbuscular mycorrhizal fungal status affects DNA methylation in seeds
Authors: Varga Sandra , Soulsbury Carl D.
Published: September 2017

Most land plants grow in association with arbuscular mycorrhizal fungi (AMF) in their roots and these fungi can cause transgenerational effects on plants' offspring. These may be caused by changes in DNA methylation of the offspring. In this study, we compared the amount of global DNA methylation in seeds of the gynodioecious plant
Geranium sylvaticum
in relation to the gender and the AMF status of the parents producing the seeds. The amount of DNA methylated was positively related to seed mass. Seeds produced by females had a similar proportion of methylated DNA regardless of the AMF status of the father siring the seed. By contrast, seeds from hermaphrodites had higher DNA methylation when sired by AMF fathers. We show to the best of our knowledge for the first time, that the AMF status of fathers can affect DNA methylation in seeds and that these changes in DNA methylation are further dependent on the gender of the mother producing the seeds.
Characterization and Pb(II) removal potential of corn straw- and municipal sludge-derived biochars
Authors: Wang Shujuan , Guo Wei , Gao Fan , Yang Rui
Published: September 2017

Corn straw- and municipal sludge-derived biochars (CS-BC and MS-BC, respectively) were used to remove Pb(II) from aqueous solutions. Despite being pyrolysed at the same temperature (723 K), MS-BC showed higher porosity and hydrophobicity than CS-BC. The optimum biochar loading and pH values allowing efficient Pb(II) removal (greater than 80%) were 0.2 g l
−1
and 7.0, respectively. The presence of PO
4
3−
(greater than 0.01 mol l
−1
) significantly affected the adsorptive performance of Pb(II) on the biochar samples. The adsorption data fitted well to a pseudo-second-order kinetic model and a Langmuir model, and the maximum Pb(II) adsorption capacities were 352 and 387 mg g
−1
for CS-BC and MS-BC, respectively. The main mechanisms involved in the adsorption of Pb(II) on biochar were electrostatic attraction and surface complexation. When comparing both biochars, CS-BC showed better cost-effectiveness for the removal of Pb(II) from aqueous solutions.
Modelling personality, plasticity and predictability in shelter dogs
Authors: Goold Conor , Newberry Ruth C.
Published: September 2017

Behavioural assessments of shelter dogs (Canis lupus familiaris) typically comprise standardized test batteries conducted at one time point, but test batteries have shown inconsistent predictive validity. Longitudinal behavioural assessments offer an alternative. We modelled longitudinal observational data on shelter dog behaviour using the framework of behavioural reaction norms, partitioning variance into personality (i.e. inter-individual differences in behaviour), plasticity (i.e. inter-individual differences in average behaviour) and predictability (i.e. individual differences in residual intra-individual variation). We analysed data on interactions of 3263 dogs (n = 19 281) with unfamiliar people during their first month after arrival at the shelter. Accounting for personality, plasticity (linear and quadratic trends) and predictability improved the predictive accuracy of the analyses compared to models quantifying personality and/or plasticity only. While dogs were, on average, highly sociable with unfamiliar people and sociability increased over days since arrival, group averages were unrepresentative of all dogs and predictions made at the individual level entailed considerable uncertainty. Effects of demographic variables (e.g. age) on personality, plasticity and predictability were observed. Behavioural repeatability was higher one week after arrival compared to arrival day. Our results highlight the value of longitudinal assessments on shelter dogs and identify measures that could improve the predictive validity of behavioural assessments in shelters.
Larval abundances of rockfishes that were historically targeted by fishing increased over 16 years in association with a large marine protected area
Authors: Thompson Andrew R. , Chen Dustin C. , Guo Lian W. , Hyde John R. , Watson William
Published: September 2017

Marine protected areas (MPAs) can facilitate recovery of diminished stocks by protecting reproductive adults. To effectively augment fisheries, however, reproductive output must increase within the bounds of MPAs so that larvae can be exported to surrounding areas and seed the region. In response to dramatic declines of rockfishes (
Sebastes
spp.) in southern California by the late 1990s two large MPAs, the Cowcod Conservation Areas (CCAs), were established in 2001. To evaluate whether the CCAs affected rockfish productivity we evaluated the dynamics of 8 species that were, and 7 that were not, historically targeted by fishing. Abundances of 6/8 targeted and 4/7 non-targeted species increased regionally from 1998 to 2013. These upturns were probably affected by environmental conditions in addition to changes in fishing pressure as the presence of most species correlated negatively with temperature, and temperature was lower than the historic average in 11/15 years. Seventy-five per cent of the targeted, but none of the non-targeted species increased at a greater rate inside than outside the CCAs while controlling for environmental factors. Results indicate that management actions, coupled with favourable environmental conditions, facilitated the resurgence of multiple rockfish species that were targeted by intense fishing effort for decades.
Flexible transparent electrodes based on silver nanowires synthesized via a simple method
Authors: Li De , Han Tao , Zhang Lei , Zhang Huai , Chen Hui
Published: September 2017

Silver nanowires (Ag NWs) with the length of approximately 60 µm and the diameter of approximately 300 nm are prepared via a simple, cost-effective, high-yield and eco-friendly procedure under a high molar concentration ratio of silver nitrate (AgNO
3
) solution to poly(vinyl pyrrolidone) solution. The pre-synthesized Ag NWs were analysed by scanning electron microscopy, X-ray diffraction and UV–visible spectrophotometer. Furthermore, the as-prepared silver nanowires were roll-coated on the surfaces of the polyethylene terephthalate (PET) substrates. By optimizing the concentration of silver nanowire solution, the flexible Ag NW/PET transparent electrodes with a sheet resistance of 3.8 Ω sq
−1
at a transmittance of 70% can be fabricated. The results reported in this paper provide a basis for optimizing the growth of silver nanowires and performances of transparent electrodes.
Prostaglandin F2α synthase in
Trypanosoma cruzi
plays critical roles in oxidative stress and susceptibility to benznidazole
Authors: García-Huertas Paola , Mejía-Jaramillo Ana María , Machado Carlos Renato , Guimarães Anna Cláudia , Triana-Chávez Omar
Published: September 2017

Nifurtimox (Nfx) and benznidazole (Bz) are the current drugs used for the treatment of Chagas disease. The mechanisms of action and resistance to these drugs in this parasite are poorly known. Prostaglandin F2α synthase or old yellow enzyme (OYE), an NAD(P)H flavin oxidoreductase, has been involved in the activation pathway of other trypanocidal drugs such as Nfx; however, its role in the mechanism of action of Bz is uncertain. In this paper, we performed some experiments of functional genomics in the parasite
Trypanosoma cruzi
with the aim to test the role of this gene in the resistance to Bz. For this, we overexpressed this gene in sensitive parasites and evaluated the resistance level to the drug and other chemical compounds such as hydrogen peroxide, methyl methanesulfonate and gamma radiation. Interestingly, parasites overexpressing OYE showed alteration of enzymes associated with oxidative stress protection such as superoxide dismutase A and trypanothione reductase. Furthermore, transfected parasites were more sensitive to drugs, genetic damage and oxidative stress. Additionally, transfected parasites were less infective than wild-type parasites and they showed higher alteration in mitochondrial membrane potential and cell cycle after treatment with Bz. These results supply essential information to help further the understanding of the mechanism of action of Bz in
T. cruzi
.
A Cdk9-PP1 kinase-phosphatase switch regulates the elongation-termination transition of RNA polymerase II
Authors: Parua Pabitra K. , Booth Gregory T. , Sansó Miriam , Benjamin Bradley , Tanny Jason C. , Lis John T. , Fisher Robert P.
Published: September 2017

The end of the RNA polymerase II (Pol II) transcription cycle is strictly regulated to ensure proper mRNA maturation and prevent interference between neighboring genes1. Pol II slowing downstream of the cleavage and polyadenylation signal (CPS) leads to recruitment of cleavage and polyadenylation factors and termination2, but how this chain of events is initiated remains unclear. In a chemical-genetic screen, we identified protein phosphatase 1 (PP1) isoforms as substrates of human positive transcription elongation factor b (P-TEFb), the cyclin-dependent kinase 9 (Cdk9)-cyclin T1 complex3. Here we show that Cdk9 and PP1 govern phosphorylation of the conserved transcription factor Spt5 in the fission yeastSchizosaccharomyces pombe. Cdk9 phosphorylates both Spt5 and a negative regulatory site on the PP1 isoform Dis24. Sites phosphorylated by Cdk9 in the Spt5 carboxy-terminal domain (CTD) are dephosphorylated by Dis2in vitro, and Cdk9 inhibitionin vivoleads to rapid Spt5 dephosphorylation that is retarded by concurrent Dis2 inactivation. Chromatin immunoprecipitation and sequencing (ChIP-seq) analysis indicates that Spt5 is dephosphorylated as transcription complexes traverse the CPS, prior to or concomitant with slowing of Pol II5. A Dis2-inactivating mutation stabilizes Spt5 phosphorylation (pSpt5) on chromatin, promotes transcription beyond the normal termination zone detected by precision run-on transcription and sequencing (PRO-seq)6, and is suppressed by ablation of Cdk9 target sites in Spt5. These results support a model whereby the transition of Pol II from elongation to termination is regulated by opposing activities of Cdk9 and Dis2 towards their common substrate Spt5—a bistable switch analogous to a Cdk1-PP1 module that controls mitotic progression4.
Harnessing the adaptive potential of mechanoresponsive proteins to overwhelm pancreatic cancer dissemination and invasion
Authors: Surcel Alexandra , Schiffhauer Eric , Thomas Dustin , Zhu Qingfeng , DiNapoli Kathleen , Herbig Maik , Otto Oliver , Guck Jochen , Jaffee Elizabeth , Iglesias Pablo , Anders Robert , Robinson Douglas
Published: September 2017

Metastatic disease is often characterized by altered cellular contractility and deformability, lending cells and groups of cells the flexibility to navigate through different microenvironments. This ability to change cell shape is driven in large part by the structural elements of the mechanobiome, which includes cytoskeletal proteins that sense and respond to mechanical stimuli. Here, we demonstrate that key mechanoresponsive proteins (those which accumulate in response to mechanical stress), specifically nonmuscle myosin IIA and IIC, α-actinin 4, and filamin B, are highly upregulated in pancreatic ductal adenocarcinoma cancer (PDAC) and in patient-derived pancreatic cancer cell lines. Their less responsive sister paralogs (myosin IIB, α-actinin 1, and filamin A) show a smaller dynamic range or disappear with PDAC progression. We demonstrate that these mechanoresponsive proteins directly impact cell mechanics using knock-down and overexpression cell lines. We further quantify the nonmuscle myosin II family members in patient-derived cell lines and identify a role for myosin IIC in the formation of transverse actin arcs in single cells and cortical actin belts in tissue spheroids. We harness the upregulation of myosin IIC and its impact of cytoskeletal architecture through the use of the mechanical modulator 4-hydroxyacetophenone (4-HAP), which increases myosin IIC assembly and stiffens cells. Here, 4-HAP decreases dissemination, induces cortical actin belts, and slows retrograde actin flow in spheroids. Finally, mice having undergone hemi-splenectomies with PDAC cells and then treated with 4-HAP have a reduction in liver metastases. Thus, increasing the activity of these mechanoresponsive proteins (in this case, by increasing myosin IIC assembly) to overwhelm the ability of cells to polarize and invade may be an effective strategy to improve the five-year survival rate of pancreatic cancer patients, currently hovering around 6%.
The Cell-Cycle Transcriptional Network Generates and Transmits a Pulse of Transcription Once Each Cell Cycle
Authors: Cho Chun-Yi , Kelliher Christina M. , Haase Steven B.
Published: September 2017

Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. However, the precise mechanisms by which these components function together in the gene regulatory network remain unclear. Here we show that the TF network can generate and transmit a “pulse” of transcription independently of CDK oscillations. The premature firing of the transcriptional pulse is prevented by early G1 inhibitors, including transcriptional corepressors and the E3 ubiquitin ligase complex APCCdh1. We demonstrate that G1 cyclin-CDKs facilitate the activation and accumulation of TF proteins in S/G2/M phases through inhibiting G1 transcriptional corepressors (Whi5 and Stb1) and APCCdh1, thereby promoting the initiation and propagation of the pulse by the TF network. These findings suggest a unique oscillatory mechanism in which global phase-specific transcription emerges from a pulse-generating network that fires once-and-only-once at the start of the cycle.
CXCR4-associated depletion of bone marrow CD34+cells following CCR5-tropic HIV-1 infection of humanized NOD/SCID/JAK3nullmice and partial protection of those cells by a promotor-targeting shRNA
Authors: Tsukamoto Tetsuo
Published: September 2017

Objectives

Hematological abnormalities that include changes in bone marrow, such as in anemia and pancytopenia, are common among human immunodeficiency virus (HIV)-infected patients, particularly in the advanced stage of disease. This study aimed to provide better experimental evidence of such manifestations in animal models.

Design

NOD/SCID/JAK3null(NOJ) mice were transplanted with human cord-derived CD34+cells with or without transduction with a lentiviral vector expressing a promoter-targeting shRNA called PromA.

Methods

At 16 weeks after transplantation, mice engrafted with CD34+cells were infected with CCR5-tropic HIV-1JRFL.

Results

At week 2 post infection, HIV replication was observed in peripheral blood mononuclear cells and splenocytes. In mice transplanted with unmanipulated CD34+cells, viral replication was accompanied by a loss of peripheral/spleen CD4+CCR5+T cells. Interestingly, bone marrow CD34+cells in HIV-infected mice were also depleted, but in a CXCR4-associated manner. Conversely, the lentiviral transfer of PromA in CD34+cells prior to transplantation rendered the humanized NOJ mice resistant to HIV replication in CD4+T cells, resulting in better preservation of peripheral/spleen CD4+CCR5+T cells and bone marrow CD34+cells at two weeks after infection.

Conclusions

These results implicate the importance of evaluating hematopoietic stem/progenitor cell pools in addition to peripheral CD4+T-cell counts to assess the early stage of HIV infection. Moreover, stable gene transfer of PromA to hematopoietic stem cells not only limited HIV replication but also led to preservation of different subsets of hematopoietic cells, including bone marrow stem/progenitor cells.
The gateway into Remote Oceania: new insights from genome-wide data
Authors: Pugach Irina , Duggan Ana T. , Merriwether D. Andrew , Friedlaender Françoise R. , Friedlaender Jonathan S. , Stoneking Mark
Published: September 2017

A widely accepted two-wave scenario of human settlement of Oceania involves the first out-of-Africa migration ca 50,000 ya, and one of the most geographically-widespread dispersals of people, known as the Austronesian expansion, which reached the Bismarck Archipelago by about 3,450 ya. While earlier genetic studies provided evidence for extensive sex-biased admixture between the incoming and the indigenous populations, some archaeological, linguistic and genetic evidence indicates a more complicated picture of settlement. To study regional variation in Oceania in more detail, we have compiled a genome-wide dataset of 823 individuals from 72 populations (including 50 populations from Oceania) and over 620,000 autosomal SNPs. We show that the initial dispersal of people from the Bismarck Archipelago into Remote Oceania occurred in a “leapfrog” fashion, completely by-passing the main chain of the Solomon Islands, and that the colonization of the Solomon Islands proceeded in a bi-directional manner. Our results also support a divergence between western and eastern Solomons, in agreement with the sharp linguistic divide known as the Tryon-Hackman line. We also report substantial post-Austronesian gene flow across the Solomons. In particular, Santa Cruz (in Remote Oceania) exhibits extraordinarily high levels of Papuan ancestry that cannot be explained by a simple bottleneck/founder event scenario. Finally, we use simulations to show that discrepancies between different methods for dating admixture likely reflect different sensitivities of the methods to multiple admixture events from the same (or similar) sources. Overall, this study points to the importance of fine-scale sampling to understand the complexities of human population history.
Effects of multiple sources of genetic drift on pathogen variation within hosts
Authors: Kennedy David A. , Dwyer Greg
Published: September 2017

Changes in pathogen genetic variation within hosts alter the severity and spread of infectious diseases, with important implications for clinical disease and public health. Genetic drift may play a strong role in shaping pathogen variation, but analyses of drift in pathogens have oversimplified pathogen population dynamics, either by considering dynamics only at a single scale (within hosts, between hosts), or by making drastic simplifying assumptions (host immune systems can be ignored, transmission bottlenecks are complete). Moreover, previous studies used genetic data to infer the strength of genetic drift, whereas we test whether the genetic drift imposed by pathogen population processes can be used to explain genetic data. We first constructed and parameterized a mathematical model of gypsy moth baculovirus dynamics that allows genetic drift to act within and between hosts. We then quantified the genome-wide diversity of baculovirus populations within each of 143 field-collected gypsy moth larvae using Illumina sequencing. Finally, we determined whether the genetic drift imposed by host-pathogen population dynamics in our model explains the levels of pathogen diversity in our data. We found that when the model allows drift to act at multiple scales, including within hosts, between hosts, and between years, it can accurately reproduce the data, but when the effects of drift are simplified by neglecting transmission bottlenecks and stochastic variation in virus replication within hosts, the model fails. Ade novomutation model and a purifying selection model similarly fail to explain the data. Our results show that genetic drift can play a strong role in determining pathogen variation, and that mathematical models that account for pathogen population growth at multiple scales of biological organization can be used to explain this variation.
The foraging perspective on economic choice
Authors: Hayden Benjamin Y.
Published: September 2017

Foraging theory offers an alternative foundation for understanding economic choice, one that sees economic choices as the outcome of psychological processes that evolved to help our ancestors search for food. Most of the choices encountered by foragers are between pursuing an encountered prey (accept) or ignoring it in favor of continued search (reject). Binary choices, which typically occur between simultaneously presented items, are special case, and are resolved through paired alternating accept-reject decisions limited by the narrow focus of attention. The foraging approach also holds out promise for helping to understand self-control and invites a reconceptualization of the mechanisms of binary choice, the relationship between choosing and stopping, and of the meaning of reward value.

Highlights

Foraging provides a basis for modeling economic choice based on adaptiveness

Foraging choices are accept-reject; foraging models interpret binary choice accordingly

The foraging view offers a different perspective on self-control decisions

Economic and stopping decisions may have a common basis
Value co-creation in the beverage and food industry
Authors: Tardivo Giuseppe , Thrassou Alkis , Viassone Milena , Serravalle Francesca
Published: September 2017

Purpose

The purpose of this paper is to define and describe how consumers may constitute an integral part of small and medium enterprises’ (SMEs) value co-creation process in the food and beverage (F&B) industry, and to provide practicable implementation recommendations to firms in the Piedmont region that are important and prominent in this sector.

Design/methodology/approach

The research methodology rests on a multiple case study design, applied to three F&B Piedmont SMEs that produce beer, water and starters: Baladin, Lurisia and Galfré.

Findings

Results show an increasing awareness by firms of the important role played by customers in value co-creation, though limited to specific roles in the case of SMEs.

Research limitations/implications

The research is limited by its exploratory nature, though the findings and conclusions drawn provide a solid foundation for further development and testing on the subject.

Practical implications

The case studies’ results allow the reader to understand the importance of the increasing awareness of the role played by customers in value co-creation, especially on the WWB, where costs are minimizing.

Originality/value

The research’s value stems from fact that there are few existing studies on the ways to engage customers in value co-creation. Moreover, these studies, contrary to the present research, are largely theoretical and either have no direct applicability or are limited to a single case.
Openness and collaboration in the food sector: mapping the field
Authors: Procopio Schoen Ana
Published: September 2017

Purpose

Research in institutional openness and collaboration-based innovation has advanced considerably in the last decade. The complexity and heterogeneity of innovation, however, turn the one-fits-all approach questionable and unveil the need to address several and different settings and industries. The purpose of this paper is to address this demand by mapping the themes covered in the research under the collaborative innovation umbrella having specifically the food and drink sector as a context.

Design/methodology/approach

The paper is based on secondary data sources, namely, a literature review of open innovation in the food and beverage (F&B) sector.

Findings

This paper builds upon a framework to classify the extant research in open innovation in the food industry and position the advancements in comparison to the general literature in the field. The categorization of the publications shows that topics like the role of networks, innovation systems, user-innovation and research and development alliances have attracted mostly attention so far, but there is still a demand for deeper and more comprehensive investigations. The field would also profit from inquiries that deal with mindset and managerial capabilities, cross-industry partnerships, converging value chains and globalization of innovation, among others.

Originality/value

To the authors’ knowledge, this is among the first papers to map research topics and research designs that have been covered to date on the field of open and collaborative innovation in the F&B industry.