bluuebunny/crossref_metadata_2025 huggingface dataset:
Nourishing Environments, Caring Cities: Gardening and the Social Reproduction of the Urban Environment in Deindustrial Michigan
Authors: Maurer Megan
Published: September 2020

Through vegetable gardening, residents of a small city in Michigan, USA, are striving to make their urban environments more socially equitable and ecologically sustainable. While gardeners across differences of class and race are motivated by a desire to change their environments and educate others, they do so in distinct ways due to different priorities. These range from neighborhood upkeep to ecological sustainability, and variation aligns with existing, intersecting forms of class distinction and racial differentiation. To engage the shared desires for equitable and sustainable urban life motivating gardeners, together with the class‐ and race‐based inequalities that shape and are shaped by their practices, this paper analyzes gardening as a form of social reproduction of the urban environment. Drawing on interviews and participant observation, this research examines the differences between gardens created for neighborhood upkeep as compared to those created for ecological sustainability, finding identifiable differences in gardening methods, spatial forms, and aesthetics directly related to gardeners’ motivations as they are shaped by experiences of race and class inequality. As both climate change and public disinvestment in social reproduction continue, the experiences of these gardeners indicate the insufficiency of shared motivations in realizing needs for just sustainability, and the importance of recognizing and responding to manifestations of social and environmental inequality in gardening motivation and practice.
Peri‐implant bone alterations under the influence of abutment screw preload stress. A preclinical vivo study
Authors: Al‐Omari Farah A. , Nagasawa Masako , Suliman Mubarak , Khraisat Ameen , Uoshima Katsumi
Published: September 2020

Objectives

The study purpose was to examine peri‐implant bone alternations around osseointegrated implants caused solely by abutment screw preload stress using different tightening torque values.

Materials and methods

Twenty 20‐ to 22‐week‐old Japanese white rabbits received two implants each in right and left femurs. Implants were randomly assigned to one of three tightening torque groups or the control (Cont) group. After 8 weeks, 35 Ncm torque was delivered to abutment screws in the recommended torque (RT) group (n = 16). Other screws received 70 Ncm torque as the high torque (HT) group (n = 16). Temporary tightening (TT) groups (n = 8) received only 70 Ncm torque without preload stress as screws were untightened immediately. Cont group (n = 40) remained in situ. Animals were euthanized at 4, 6, 8, and 10 weeks after torque application. Micro‐CT images were then taken, and undecalcified ground sections were stained with toluidine blue.

Results

Cross‐sections of cortical bone showed remodeling activities adjacent to the implant in all groups. While bone marrow spaces appearance was relatively small in Cont and TT groups, RT and HT groups showed large bone marrow spaces and extensive remodeling activity. Bone‐to‐implant contact was significantly less in RT and HT groups compared with Cont and TT groups at different time points (p ˂ .05). Furthermore, RT and HT groups showed significantly less bone volume and area (p ˂ .05).

Conclusion

Results suggested that preload stress without any occlusal loading might negatively affect peri‐implant bone stability and initiate bone remodeling. This could alter bone mechanical properties, subsequently influencing long‐term implant success.
Sublingual immunotherapy vs placebo in the management of grass pollen‐induced allergic rhinitis in adults: A systematic review and meta‐analysis
Authors: Boldovjáková Dominika , Cordoni Sara , Fraser Craig John , Love Aimee Beth , Patrick Lorna , Ramsay Gary James , Ferguson Aaron Stephen James , Gomati Anas , Ram Bhaskar
Published: September 2020

Introduction

Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa affecting approximately 20% of the population worldwide. Current therapies include intranasal antihistamines, corticosteroids, subcutaneous and sublingual immunotherapy (SLIT). This review and meta‐analysis assess the efficacy of SLIT in the management of grass pollen‐induced AR in adults.

Methods

Ovid EMBASE, Ovid EBM Reviews, Cochrane Central Register of Controlled Trials, Ovid MedLine and PubMed were searched using the following terms: ‘sublingual immunotherapy’, ‘SLIT’, ‘rhinitis’, ‘allergic rhinitis’, ‘rhinosinusitis’ and ‘rhino‐conjunctivitis’. All included studies were double‐blind, placebo‐controlled and randomised trials. Primary outcome was symptom score and secondary outcome included quality of life and safety profile. Meta‐analysis of symptom improvement was carried out.

Results

Six studies were identified with 979 subjects randomly allocated to SLIT and 992 to a placebo control. All studies reported an improvement in symptoms with SLIT, with five reaching statistical significance (P < .05). Four studies reported statistically significant improvement in quality of life (P < .05). Oral pruritus was the most common adverse event reported. The overall risk of bias was high in 50% of the studies.

Conclusions

Sublingual immunotherapy was a safe and effective treatment for grass pollen‐induced AR in adults, and therefore, consideration should be given to its use for moderate‐to‐severe disease in the UK‐wide population.
Comparative study of microvascular function: Forearm blood flow versus dynamic retinal vessel analysis
Authors: Schirutschke Holger , Kochan Johannes , Haink Kristin , Rettig Ronny , Parmentier Simon Paul , Ziemssen Tjalf , Passauer Jens
Published: September 2020

Objective

Recently, dynamic retinal vessel analysis (DVA) has gained interest for investigation of microvascular function but comparative measurements with standard methods like the forearm blood flow technique (FBF) are uncommon till now.

Methods

We recruited 23 high‐risk cardiovascular patients (Risk) and 17 healthy persons (Ctrl). During the FBF experiment, postocclusive reactive hyperaemia (RH) as well as endothelium‐dependent and independent vasodilation was measured by infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) into the brachial artery. The dynamic vessel analyzer was applied for measurement of the retinal arterial and venous response to flickering light during DVA and for determination of the central retinal arterial (CRAE) and venous equivalent (CRVE).

Results

Forearm blood flow technique was significantly attenuated in the patient group during postocclusive RH (p < .005). The increase of FBF in response to SNP did not differ significantly between the two groups (p = .09). In contrast, the FBF response to ACh was significantly blunted in the patient group (p < .05), indicating endothelial dysfunction. DVA did not detect any difference of retinal arterial (p = .68) or retinal venous (p = .93) vasodilation between both groups. The CRAE (p = .55) and CRVE (p = .83) did not differ significantly in either group.

Conclusions

Forearm blood flow and DVA cannot be regarded as equivalent methods for testing of microvascular function. Possible explanations include differences in the vascular beds and vessel diameters examined as well as differences in the trigger mechanisms applied. Further studies are needed to define the role of DVA in this context.
Chromatin‐modifying drugs and metabolites in cell fate control
Authors: Yao Ziyue , Chen Yu , Cao Wenhua , Shyh‐Chang Ng
Published: September 2020

For multicellular organisms, it is essential to produce a variety of specialized cells to perform a dazzling panoply of functions. Chromatin plays a vital role in determining cellular identities, and it dynamically regulates gene expression in response to changing nutrient metabolism and environmental conditions. Intermediates produced by cellular metabolic pathways are used as cofactors or substrates for chromatin modification. Drug analogues of metabolites that regulate chromatin‐modifying enzyme reactions can also regulate cell fate by adjusting chromatin organization. In recent years, there have been many studies about how chromatin‐modifying drug molecules or metabolites can interact with chromatin to regulate cell fate. In this review, we systematically discuss how DNA and histone‐modifying molecules alter cell fate by regulating chromatin conformation and propose a mechanistic model that explains the process of cell fate transitions in a concise and qualitative manner.
Gender differences in heart transplantation: Twenty‐five year trends in the nationwide Spanish heart transplant registry
Authors: García‐Cosío María D. , González‐Vilchez Francisco , López‐Vilella Raquel , Barge‐Caballero Eduardo , Gómez‐Bueno Manuel , Martínez‐Selles Manuel , Arizón Jose M. , Rangel Sousa Diego , González‐Costello José , Mirabet Sonia , Pérez‐Villa Félix , Díaz‐Molina Beatriz , Rábago Gregorio , Portolés Ocampo Ana , de la Fuente‐Galán Luis , Garrido Iris , Delgado‐Jiménez Juan F.
Published: September 2020

The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their evolution in a study covering the years 1993–2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25‐year study period. HT rate was higher in men, although this decreased over the 25‐year study period. Type of heart disease differed in men versus women (p < .001): ischemic heart disease 47.6% versus 22.5%, dilated cardiomyopathy 41.3% versus 34.6%, or other 36% versus 17.8%, respectively. Men were more frequently diabetics (18% vs. 13.1% p < .001), hypertensives (33.1% vs. 24% p < .001), and smokers (21.7% vs. 12.9% p < .001), respectively. Women had more pre‐HT malignancies (7.1% vs. 2.8% p < .001), and their clinical status was worse at HT due to renal function and mechanical ventilation. Adjusted survival (p = .198) and most of the mortality‐related variables were similar in men and women. Death occurred more frequently in women due to rejection (7.9% vs. 5.1% p < .001) and primary failure (18.2% vs. 12.5% p < .001) and in men due to malignancies (15.1% vs. 6.6% p < .001).
Outpatient COVID‐19 surveillance testing in orthotopic heart transplant recipients
Authors: Carey Sandra A. , Afzal Aasim , Jamil Aayla , Williams Sarah , Gottlieb Robert L.
Published: September 2020

COVID‐19 case fatality rate in the United States is currently reported at 4.8% based on the confirmed cases of COVID‐19. However, there are conflicting reports of estimated deaths in the post‐cardiac transplantation patient population associated with COVID‐19.

Methods

Observational, retrospective analysis of a large cohort of post Orthotopic Heart Transplantation (OHT) patients in a high volume heart transplantation program in Dallas, Texas underwent outpatient COVID‐19 screening and testing for both SARS‐CoV‐2 nasopharyngeal RT‐PCR and anti‐SARS‐CoV2 IgG serology as a result of a clinic protocol to facilitate re‐opening of face‐to‐face outpatient clinical visits.

Results

The full outpatient cohort tested at time of their clinic visit tested negative for COVID‐19 by nasopharyngeal RT‐PCR. Only 2 patients tested seropositive for anti‐SARS‐COV2 IgG. Five positive inpatient cases were also identified and all, but one recovered.

Conclusion

A COVID‐19 surveillance protocol can be easily instituted in this high‐risk population and facilitate safe transplant clinic operation. As the cases and prevalence increase across the United States, further strategies will need to be developed to determine the best course of action to help manage this select population while minimizing their exposure to the ongoing pandemic.
Factors influencing cognitive outcome in opsoclonus–myoclonus syndrome
Authors: Hukin Juliette
Published: September 2020

This commentary is on the original article by Sheridan et al. on pages 1444–1449 of this issue.
Efficacy and safety of a sodium‐glucose co‐transporter‐2 inhibitor versus placebo as an add‐on therapy for people with type 2 diabetes inadequately treated with metformin and a dipeptidyl peptidase‐4 inhibitor: a systematic review and meta‐analysis of randomised controlled trials
Authors: De Buitléir C. , O’ Connor E. , Satti M. M. , Shaw J. , Liew A.
Published: September 2020

Aims

To conduct a systematic review and meta‐analysis to assess the efficacy, safety and tolerability of sodium‐glucose co‐transporter‐2 inhibitors vs placebo as add‐on therapy after metformin and dipeptidyl peptidase‐4 inhibitor dual therapy in type 2 diabetes.

Methods

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines (PROSPERO registration number: CRD42018099398). A search was conducted via PubMed, www.clinicaltrials.gov and Cochrane Central Register of Controlled Trials of relevant randomised controlled trials up until 14 August 2020 that compared sodium‐glucose co‐transporter‐2 inhibitors vs placebo as add‐on therapy after metformin and dipeptidyl peptidase‐4 inhibitor therapy. A random‐effects model was used.

Results

Six randomised controlled trials (1661 participants) met the inclusion criteria. Compared with placebo, sodium‐glucose co‐transporter‐2 inhibitor treatment, as add‐on to metformin and dipeptidyl peptidase‐4 inhibitor therapy, was associated with a significant reduction in HbA1c level [mean difference –8 mmol/mol, 95% CI –10, –6 (–0.7%, 95% CI –0.9, –0.6); P < 0.00001], in fasting plasma glucose level [mean difference –1.70 mmol/l, 95% CI –1.91, –1.49; P < 0.00001], in weight (mean difference –1.76 kg, 95% CI –2.04, –1.48; P < 0.00001) and in blood pressure (systolic blood pressure: mean difference –3.6 mmHg, 95% CI –4.8, –2.4; P < 0.00001; diastolic blood pressure: mean difference –1.5 mmHg; 95% CI –2.4, –0.6; P = 0.002). Genital mycotic infections (odds ratio 7.37, 95% CI 3.06, 17.76; P < 0.00001) were more common with sodium‐glucose co‐transporter‐2 inhibitors, but there was no significant statistical difference in urinary tract infections (odds ratio 1.16, 95% CI 0.63, 2.13; P = 0.64), in hypoglycaemia (odds ratio 1.36, 95% CI 0.61, 3.04; P = 0.45), or in discontinuation rates due to adverse events (odds ratio 1.52, 95% CI 0.78, 2.97; P = 0.22) between the two groups.

Conclusions

In comparison with placebo, add‐on therapy with a sodium‐glucose co‐transporter‐2 inhibitor is significantly more efficacious in lowering HbA1c, fasting plasma glucose and weight in people with type 2 diabetes following inadequate glycaemic control with metformin and a dipeptidyl peptidase‐4 inhibitor. The rate of discontinuation due to adverse events was similar despite higher risk of genital mycotic infections.
Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle
Authors: Döbrössy Máté D. , Ramanathan Chockalingam , Ashouri Vajari Danesh , Tong Yixin , Schlaepfer Thomas , Coenen Volker A.
Published: September 2020

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.
Phase‐amplitude coupling profiles differ in frontal and auditory cortices of bats
Authors: García‐Rosales Francisco , López‐Jury Luciana , González‐Palomares Eugenia , Cabral‐Calderín Yuranny , Kössl Manfred , Hechavarria Julio C.
Published: September 2020

Neural oscillations are at the core of important computations in the mammalian brain. Interactions between oscillatory activities in different frequency bands, such as delta (1–4 Hz), theta (4–8 Hz) or gamma (>30 Hz), are a powerful mechanism for binding fundamentally distinct spatiotemporal scales of neural processing. Phase‐amplitude coupling (PAC) is one such plausible and well‐described interaction, but much is yet to be uncovered regarding how PAC dynamics contribute to sensory representations. In particular, although PAC appears to have a major role in audition, the characteristics of coupling profiles in sensory and integration (i.e. frontal) cortical areas remain obscure. Here, we address this question by studying PAC dynamics in the frontal‐auditory field (FAF; an auditory area in the bat frontal cortex) and the auditory cortex (AC) of the bat Carollia perspicillata. By means of simultaneous electrophysiological recordings in frontal and auditory cortices examining local‐field potentials (LFPs), we show that the amplitude of gamma‐band activity couples with the phase of low‐frequency LFPs in both structures. Our results demonstrate that the coupling in FAF occurs most prominently in delta/high‐gamma frequencies (1‐4/75‐100 Hz), whereas in the AC the coupling is strongest in the delta‐theta/low‐gamma (2‐8/25‐55 Hz) range. We argue that distinct PAC profiles may represent different mechanisms for neuronal processing in frontal and auditory cortices, and might complement oscillatory interactions for sensory processing in the frontal‐auditory cortex network.
The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers
Authors: Kruijt N. , van den Bersselaar L. R. , Kamsteeg E. J. , Verbeeck W. , Snoeck M. M. J. , Everaerd D. S. , Abdo W. F. , Jansen D. R. M. , Erasmus C. E. , Jungbluth H. , Voermans N. C.
Published: September 2020

Background and purpose

Rhabdomyolysis is a medical emergency characterized by acute skeletal muscle breakdown with a sudden rise and subsequent fall of serum creatine kinase (CK) levels. Rhabdomyolysis events are provoked by exposure to external triggers, possibly in combination with an increased genetic susceptibility. We aimed to describe comprehensively the external triggers and potentially pathogenic genetic variants possibly implicated in increased rhabdomyolysis susceptibility.

Methods

We performed a retrospective single‐center study, including a total of 1302 patients with an acute CK level exceeding 2000 IU/l.

Results

Anoxia was the most frequently reported trigger (40%). A subset of 193 patients were clinically suspected of an underlying genetic disorder (recurrent episodes, a positive family history, very high or persistently increased CK levels). In 72 of these patients, an unequivocal genetic defect was identified. A total of 22 genes with pathogenic variants were identified, including 52 different variants. Of those, 11 genes have been previously associated with rhabdomyolysis (ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, RYR1). Eleven genes are probably implicated in increased susceptibility (including AGL, CAPN3, CNBP, DMPK, MAGT1, ACADM, SCN4A, SGCA, SGCG, SMPD1, TANGO2).

Conclusion

These findings suggest that the spectrum of genetic susceptibility for rhabdomyolysis has not yet been completely clarified. With the increasing availability of next‐generation sequencing in a diagnostic setting, we expect that in more cases a genetic defect will be identified.
Cardiovascular disease, psychiatric diagnosis and sex differences in the multistep hypothesis of amyotrophic lateral sclerosis
Authors: Garton F. C. , Trabjerg B. B. , Wray N. R. , Agerbo E.
Published: September 2020

Background and purpose

Amyotrophic lateral sclerosis (ALS) risk increases with age, and a linear log‐incidence and log‐age relationship is interpreted to suggest that five to six factors are involved in disease onset. The factors remain unidentified, except that fewer steps are predicted for those carrying a known ALS‐causing mutation.

Methods

Men with a psychiatric disorder or cardiovascular disease (CVD) diagnosis have an increased relative risk of ALS. Using the Danish population registries and ALS diagnosis years 1980 to 2017, we tested whether these factors would decrease the predicted steps to disease.

Results

Consistent with previous reports, we find a linear log‐incidence and log‐age ALS‐onset relationship (n = 4385, regression coefficient b = 4.6, 95% confidence interval [CI]: 4.3–4.9, R2 = 0.99). This did not differ when considering ALS cases with a prior psychiatric diagnosis (n = 391, b = 4.6, 95% CI: 4.0–5.1) Surprisingly, it was higher (+1.5 steps, P = 2.3 × 10−5) for those with a prior CVD diagnosis (n = 901, b = 6.1, 95% CI: 5.4–6.8). To control for competing risk of death, a test to investigate if this effect was maintained in those with CVD in the population demonstrated an increased baseline risk and fewer steps to disease (b = 1.8, 95% CI: 1.2–2.3, P = 4.6 × 10−21), which consistent with a positive association of CVD and ALS. Assessing sex differences, our data and meta‐analyses (n = 22 495) support half a step fewer for men (−0.4, 95% CI: ±0.24, P = 0.00031) without support for contributing differences explained by menopause.

Conclusions

Any factor associated with ALS disease onset may be relevant for understanding disease pathogenesis and/or counselling. Modelling disease incidence with age demonstrates some insight into relevant risk factors; however, the outcome can differ if competing risks are considered.
Cardiac sources of cerebral embolism in people with migraine
Authors: De Giuli V. , Grassi M. , Locatelli M. , Gamba M. , Morotti A. , Bonacina S. , Mazzoleni V. , Pezzini D. , Magoni M. , Monastero R. , Padovani A. , Pezzini A.
Published: September 2020

Background and purpose

Whether the reported association between migraine with aura (MA) and cardioembolic stroke may be explained by a higher rate of atrial fibrillation (AF) or by other potential cardiac sources of cerebral embolism remains to be determined.

Methods

In the setting of a single centre cohort study of consecutive patients with acute brain ischaemia stratified by migraine status, the association between AF as well as patent foramen ovale (PFO) and migraine was explored.

Results

In all, 1738 patients (1017 [58.5%] men, mean age 67.9 ± 14.9 years) qualified for the analysis. Aging was inversely associated with migraine, whilst women had a >3‐fold increased disease risk (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.58–5.66). No association between AF and history of migraine or its pathogenic subtypes was detected. Conversely, migraine was associated with PFO, both in the entire cohort (OR 1.84, 95% CI 1.07–3.16) and in patients aged ≤55 years (OR 2.21, 95% CI 1.16–4.22). This association was significant for MA (OR 2.92, 95% CI 1.32–6.45 in the entire cohort; OR 2.92, 95% CI 1.15–7.41 in patients aged ≤55 years) and in women (OR 8.23, 95% CI 2.06–32.77), but not for migraine without aura.

Conclusions

In patients with brain ischaemia migraine is not associated with AF. Conversely, there is a probable relation between migraine, especially MA, and PFO in patients who are younger and have a more favourable vascular risk factor profile, and in women.
Exercise‐associated rhythm disturbances in poorly performing Thoroughbreds: risk factors and association with racing performance
Authors: Marr Celia M. , Franklin Samantha , Garrod Georgie , Wylie Claire , Smith Lewis , Dukes‐McEwan Jo , Bright Jan , Allen Kate
Published: September 2020

Background

Exercise‐associated cardiac rhythm disturbances are common, but there is a lack of evidence‐based criteria on which to distinguish clinically relevant rhythm disturbances from those that are not.

Objectives

To describe and characterise rhythm disturbances during clinical exercise testing; to explore potential risk factors for these rhythm disturbances and to determine whether they influenced future racing.

Study design

Retrospective cohort using a convenience sample.

Methods

Medical records were reviewed from two clinical services to identify horses with poor performance and/or respiratory noise with both exercise endoscopy and electrocardiography results. Respiratory and ECG findings recorded by the attending clinicians were described, and for polymorphic ventricular rhythms (n = 12), a consensus team agreed the final rhythm characterisation. Several statistical models analysing risk factors were built and racing records were reviewed to compare horses with and without rhythm disturbance.

Results

Of 245 racehorses, 87 (35.5%) had no ectopic/re‐entrant rhythms, 110 (44.9%) had isolated premature depolarisations during sinus rhythm and 48 (19.6%) horses had complex tachydysrrythmias. Rhythm disturbances were detected during warm‐up in 20 horses (8.2%); during gallop in 61 horses (24.9%) and during recovery in 124 horses (50.6%). Most complex rhythm events occurred during recovery, but there was one horse with a single couplet during gallop and another with a triplet during gallop. Fifteen horses (one with frequent isolated premature depolarisations and 14 complex rhythms) were considered by clinicians to be potentially contributing to poor performance. Treadmill exercise tests, the presence of exercise‐associated upper respiratory tract obstructions and National Hunt racehorses were associated with rhythm disturbances. The proportion of horses racing again after diagnosis (82%) was similar in all groups and univariable analysis revealed no significant associations between subsequent racing and the presence of any ectopic/re‐entrant rhythm, or the various sub‐groups based on phase of exercise in which this was detected.

Main limitations

Reliance on retrospective data collection from medical records with no control group. Exercise ECGs were collected using only 1 or 2 leads. Variables examined as risk factors could be considered to be inter‐related and our sub‐groups were small.

Conclusions

This study confirms a high prevalence of cardiac rhythm disturbances, including complex ectopic/re‐entrant rhythms, in poorly performing racehorses. Detection of rhythm disturbances may vary with exercise test conditions and exercise‐associated upper respiratory tract obstructions increase the risk of rhythm disturbances.
Markers for Ca++‐induced terminal differentiation of keratinocytes in vitro under defined conditions
Authors: Jeriha Jakob , Kolundzic Nikola , Khurana Preeti , Gordon Mitch , Celli Anna , Mauro Theodora M. , Ilic Dusko
Published: September 2020

Differentiation of normal human keratinocytes (NHK) grown in vitro as a monolayer to confluency can be triggered with an acute increase in concentration of extracellular Ca++. Over several days, induced by Ca++, the cells form pseudostratified sheets that somewhat resemble the basic organization of the intact skin. This experimental system is widely used in studies of keratinocyte biology and skin pathology. However, expression pattern of the genes considered as markers for cells in specific layers of epidermis in vivo does not always match the specific pattern observed in vitro and might lead to misinterpretation of data. Here, we demonstrate that among 18 markers of terminally differentiated keratinocytes of stratum granulosum (SG) and stratum corneum (SC) in vivo, only four (CDSN, KPRP, LCE1C and SPRR4) have reproduced their expression pattern in vitro. Our data suggest that findings based on two‐dimensional (2D) Ca++‐induced terminal differentiation of NHK in vitro should be subjected to additional scrutiny before conclusions could be made and, if possible, verified in other experimental system that might more faithfully represent the in vivo microenvironment.
The PI3Kγ/AKT signaling pathway mediates peripheral antinociceptive action of dipyrone
Authors: Cecílio Nerry T. , Souza Guilherme R. , Alves‐Filho Jose C. , Cunha Fernando Q. , Cunha Thiago M.
Published: September 2020

Dipyrone (DIP), also known as metamizole, is an over‐the‐counter analgesic used in Europe and Latin America. Evidence suggesting that inflammatory pain attenuation by DIP is associated with a direct impact on peripheral primary nociceptive neurons through the stimulation of nitric oxide signaling pathway. However, the molecular mechanism by which DIP activates this pathway remains unknown. The PI3Kγ/AKT signaling cascade activation is one of the well‐known molecular mechanisms that promote nitric oxide production in sensory neurons. Herein, we investigated the role of the PI3Kγ/AKT signaling cascade in the context of peripheral analgesic effect of DIP. DIP was administered into PGE2 pre‐sensitized paws of rats and mechanical hyperalgesia was determined using electronic von Frey test after 1 h. Nonselective or selective pharmacological inhibitors of PI3Kγ and AKT were also administered in DIP‐treated rats under paws sensitized with PGE2. Intraplantar injection of DIP attenuated PGE2‐induced hyperalgesia in a dose‐dependent manner. Treatment with nonselective (wortmannin or LY294002) or selective (AS605240) pharmacological inhibitors of PI3Kγ reduced the peripheral antihypernociceptive effect of DIP. Consistently, AKT selective inhibitor also reversed analgesic DIP effects. Corroborating these data, we found that DIP induced AKT phosphorylation in cultured dorsal root ganglion neurons, which was prevented in the presence of PI3Kγ selective inhibitor. Taken together, these findings provide evidence that peripheral analgesic effect of DIP is dependent on the activation of PI3Kγ/AKT signaling pathway.
Announcing the winners of our COVID‐19 Creative Communication Competition
Authors: Dhillon Paraminder
Published: September 2020

The FEBS Journal announces the winners and runners‐up of its COVID‐19 Creative Communication Competition in which entrants were asked to depict ‘post‐lockdown lab life’.
Vitamin D to prevent COVID‐19: recommendations for the design of clinical trials
Authors: Camargo Carlos A. , Martineau Adrian R.
Published: September 2020

The coronavirus disease 2019 (COVID‐19) pandemic has focused attention on the potential role of vitamin D supplementation to prevent COVID‐19. In this issue, Merzon and colleagues report epidemiologic data on the vitamin D status of 7807 individuals and their risk of developing COVID‐19. In multivariable analyses, low vitamin D status was associated with increased risk of both COVID‐19 infection and hospitalization. The authors call for clinical trials of vitamin D supplementation. In this Commentary, we discuss some of the challenges of vitamin D research and provide recommendations for the design of randomized controlled trials of vitamin D supplementation to prevent COVID‐19.

Comment on: https://doi.org/10.1111/febs.15495
Phosphorylated full‐length Tau interacts with 14‐3‐3 proteins via two short phosphorylated sequences, each occupying a binding groove of 14‐3‐3 dimer
Authors: Neves João Filipe , Petrvalská Olivia , Bosica Francesco , Cantrelle François‐Xavier , Merzougui Hamida , O'Mahony Gavin , Hanoulle Xavier , Obšil Tomáš , Landrieu Isabelle
Published: September 2020

Protein–protein interactions (PPIs) remain poorly explored targets for the treatment of Alzheimer’s disease. The interaction of 14‐3‐3 proteins with Tau was shown to be linked to Tau pathology. This PPI is therefore seen as a potential target for Alzheimer’s disease. When Tau is phosphorylated by PKA (Tau‐PKA), several phosphorylation sites are generated, including two known 14‐3‐3 binding sites, surrounding the phosphorylated serines 214 and 324 of Tau. The crystal structures of 14‐3‐3 in complex with peptides surrounding these Tau phosphosites show that both these motifs are anchored in the amphipathic binding groove of 14‐3‐3. However, in the absence of structural data with the full‐length Tau protein, the stoichiometry of the complex or the interface and affinity of the partners is still unclear. In this work, we addressed these points, using a broad range of biophysical techniques. The interaction of the long and disordered Tau‐PKA protein with 14‐3‐3σ is restricted to two short sequences, containing phosphorylated serines, which bind in the amphipathic binding groove of 14‐3‐3σ. Phosphorylation of Tau is fundamental for the formation of this stable complex, and the affinity of the Tau‐PKA/14‐3‐3σ interaction is in the 1–10 micromolar range. Each monomer of the 14‐3‐3σ dimer binds one of two different phosphorylated peptides of Tau‐PKA, suggesting a 14‐3‐3/Tau‐PKA stoichiometry of 2 : 1, confirmed by analytical ultracentrifugation. These results contribute to a better understanding of this PPI and provide useful insights for drug discovery projects aiming at the modulation of this interaction.
Structural snapshots of the cellular folded protein translocation machinery Bcs1
Authors: Xia Di
Published: September 2020

Proteins destined to various intra‐ and extra‐cellular locations must traverse membranes most frequently in an unfolded form. When the proteins being translocated need to remain in a folded state, specialized cellular transport machinery is used. One such machine is the membrane‐bound AAA protein Bcs1 (Bcs1), which assists the iron‐sulfur protein, an essential subunit of the respiratory Complex III, across the mitochondrial inner membrane. Recent structure determinations of mouse and yeast Bcs1 in three different nucleotide states reveal its homo‐heptameric association and at least two dramatically different conformations. The apo and ADP‐bound structures are similar, both containing a large substrate‐binding cavity accessible to the mitochondrial matrix space, which contracts by concerted motion of the ATPase domains upon ATP binding, suggesting that bound substrate could then be pushed across the membrane. ATP hydrolysis drives substrate release and resets Bcs1 conformation back to the apo/ADP form. These structures shed new light on the mechanism of folded protein translocation across a membrane, provide better understanding on the assembly process of the respiratory Complex III, and correlate clinical presentations of disease‐associated mutations with their locations in the 3D structure.
Oral proficiency levels of first‐year entering college students with and without Advanced Placement scores
Authors: Bernhardt Elizabeth B. , Leffell Cici M.
Published: September 2020

Though considerable professional discussion has focused on the integration of K–16 curricula, the level of oral proficiency with which students enter college and how that the entry level relates to college programs remains untested. The entry landscape is varied, complexified by the diverse curricula that students experience, in particular within Advanced Placement (AP) programs. The present study probes the oral proficiency levels of 2071 Spanish learners and 712 French learners. The data indicate a significant difference between the oral proficiency levels of students entering college with and without an AP score, but suggest that the difference is only one sublevel higher on the American Council on the Teaching of Foreign Languages' oral proficiency scale, from intermediate mid to intermediate high on average. The paper discusses the implications of these levels, questioning whether they meet the values of the profession, whether students with these levels are prepared for study in literature programs, and whether an investment in AP programs is prudent.
Using climate‐driven leaf phenology and growth to improve predictions of gross primary productivity in North American forests
Authors: Fang Jing , Lutz James A. , Wang Leibin , Shugart Herman H. , Yan Xiaodong
Published: September 2020

Forest ecosystems are an important sink for terrestrial carbon sequestration. Hence, accurate modeling of the intra‐ and interannual variability of forest photosynthetic productivity remains a key objective in global biology. Applying climate‐driven leaf phenology and growth in models may improve predictions of the forest gross primary productivity (GPP). We used a dynamic non‐structural carbohydrates (NSC) model (FORCCHN2) that couples leaf development and phenology to investigate the relationships among photosynthesis and environmental factors. FORCCHN2 simulates spring and autumn phenological events from heat and chilling, respectively. Leaf area index data from satellites along with climate data estimated localized phenological parameters. NSC limitation, immediate temperature, accumulated heat, and growth potential comprised a daily leaf‐growth model. Functionally, leaf growth was decoupled from photosynthesis. Leaf biomass determined overall photosynthetic production. We compared this model with outputs of the other six terrestrial biospheric models and with observations from the North American Carbon Program Site Interim Synthesis in 18 forest sites. This model improved the predicted performance of yearly GPP with a 57%–210% increase in correlation (median) and up to a 102% reduction in biases (median), compared to three prognostic models and three prescribed models. At the North America continental scale, the model predicted the average annual GPP of 7.38 Pg C/year from forest ecosystems during 1985–2016. The results showed an increasing trend of GPP in North America (1.0 Pg C/decade). The inclusion of climate‐driven phenology and growth has a significant potential for improving dynamic vegetation models, and promotes a further understanding of the complex relationship between environment and photosynthesis.
Evolutionary principles and genetic considerations for guiding conservation interventions under climate change
Authors: Gaitán‐Espitia Juan D. , Hobday Alistair J.
Published: September 2020

Impacts of climate change are apparent in natural systems around the world. Many species are and will continue to struggle to persist in their current location as their preferred environment changes. Traditional conservation efforts aiming to prevent local extinctions have focused on two aspects that theoretically enhance genetic diversity—population connectivity and population size—through ‘passive interventions’ (such as protected areas and connectivity corridors). However, the exceptionally rapid loss of biodiversity that we are experiencing as result of anthropogenic climate change has shifted conservation approaches to more ‘active interventions’ (such as rewilding, assisted gene flow, assisted evolution, artificial selection, genetic engineering). We integrate genetic/genomic approaches into an evolutionary biology framework in order to discuss with scientists, conservation managers and decision makers about the opportunities and risks of interventions that need careful consideration in order to avoid unwanted evolutionary outcomes.
Climate‐ versus geographic‐dependent patterns in the spatial distribution of macroinvertebrate assemblages in New World depressional wetlands
Authors: Stenert Cristina , Pires Mateus M. , Epele Luis B. , Grech Marta G. , Maltchik Leonardo , McLean Kyle I. , Mushet David M. , Batzer Darold P.
Published: September 2020

Analyses of biota at lower latitudes may presage impacts of climate change on biota at higher latitudes. Macroinvertebrate assemblages in depressional wetlands may be especially sensitive to climate change because weather‐related precipitation and evapotranspiration are dominant ecological controls on habitats, and organisms of depressional wetlands are temperature‐sensitive ectotherms. We aimed to better understand how wetland macroinvertebrate assemblages were structured according to geography and climate. To do so, we contrasted aquatic‐macroinvertebrate assemblage structure (family level) between subtropical and temperate depressional wetlands of North and South America using presence–absence data from 264 of these habitats across the continents and more‐detailed relative‐abundance data from 56 depressional wetlands from four case‐study locations (North Dakota and Georgia in North America; southern Brazil and Argentinian Patagonia in South America). Both data sets roughly partitioned wetland numbers equally between the two climatic zones and between the continents. We used ordination methods (PCA and NMDS) and tests of multivariate dispersion (PERMDISP) to assess the distribution and the homogeneity in variation in the composition of macroinvertebrate assemblages across climates and continents, respectively. We found that macroinvertebrate assemblage structures in the subtropical depressional wetlands of North and South America were similar to each other (at the family level), while assemblages in the North and South American temperate wetlands were unique from the subtropics, and from each other. Tests of homogeneity of multivariate dispersion indicated that family‐level assemblage structures were more homogeneous in wetlands from the subtropical than the temperate zones. Our study suggests that ongoing climate change may result in the homogenization of macroinvertebrate assemblage structures in temperate zones of North and South America, with those assemblages becoming enveloped by assemblages from the subtropics. Biotic homogenization, more typically associated with other kinds of anthropogenic factors, may also be affected by climate change.
Endogenous inclusive development of e‐commerce in rural China: A case study
Authors: Gao Ping , Liu Yajun
Published: September 2020

This paper advances understanding of the process and mechanism of endogenous inclusive development of information and communications technology (ICT) solutions. We present a case of a bottom of the pyramid (BoP) community in a rural area in China, which has achieved sustainable furniture e‐commerce development independently. The case study demonstrates that e‐commerce development in a disadvantaged area can start from a seed business model targeting a niche market with simple products, which will incur low costs and low skill requirements for entrepreneurs, and is thus able to scale up within local BoP community. In the second stage, BoP entrepreneurs must engage in intensive learning from the seed entrepreneur and other early movers to gain the required capabilities for operating the seed business model. In the last stage, BoP entrepreneurs need to focus on business model innovation and scoping, and form a local value chain and ecosystem for e‐commerce development. Throughout the e‐commerce development process, a seed entrepreneur plays specific critical roles at each stage. Practical implications for the BoP community to take advantage of ICT innovation to achieve sustainable development are given.
Overexpression of neural miRNAs miR‐9/9* and miR‐124 suppresses differentiation to Müller glia and promotes differentiation to neurons in mouse retina in vivo
Authors: Suzuki Fumiko , Okuno Mariko , Tanaka Tomoya , Sanuki Rikako
Published: September 2020

MicroRNAs (miRNAs) are known to regulate gene expression and modulate cellular differentiation. MicroRNA‐9/9* (miR‐9/9*) and microRNA‐124 (miR‐124) are highly expressed in the central nervous system. In vivo function of miR‐9/9* and miR‐124 has been investigated in detail, whereas there remain some discrepancies regarding neural development. To this end, we electroporated miR‐9/9*, miR‐124 or miR‐9/9*/124 expression plasmids into neonatal retinal progenitor cells (RPCs) in vivo and analyzed the fate of electroporated cells. Both miR‐9/9* and miR‐124 reduced the number of SOX9‐ and GS‐positive cells and increased that of TUBB3‐positive cells in the postnatal day 14 retina. No major effects on the proliferation and apoptosis of the electroporated cells were detected at least postnatal day 3. These indicated that miR‐9/9* and miR‐124 influence the cell fate of glial cells, thereby inducing their differentiation into neurons. Moreover, we found this cell fate modulation was occurred in RPCs indicating high‐level expression of miRNA, but not in the low level. Our results strongly suggest that high‐level miRNA overexpression is essential for directing cell fate by miR‐9/9* and miR‐124 interference.
Review of Laboratory Scale Models of Karst Aquifers: Approaches, Similitude, and Requirements
Authors: Mohammadi Zargham , Illman Walter A. , Field Malcolm
Published: September 2020

This review focuses on investigations of groundwater flow and solute transport in karst aquifers through laboratory scale models (LSMs). In particular, LSMs have been used to generate new data under different hydraulic and contaminant transport conditions, testing of new approaches for site characterization, and providing new insights into flow and transport processes through complex karst aquifers. Due to the increasing need for LSMs to investigate a wide range of issues, associated with flow and solute migration karst aquifers this review attempts to classify, and introduce a framework for constructing a karst aquifer physical model that is more representative of field conditions. The LSMs are categorized into four groups: sand box, rock block, pipe/fracture network, and pipe‐matrix coupling. These groups are compared and their advantages and disadvantages highlighted. The capabilities of such models have been extensively improved by new developments in experimental methods and measurement devices. Newer technologies such as 3D printing, computed tomography scanning, X‐rays, nuclear magnetic resonance, novel geophysical techniques, and use of nanomaterials allow for greater flexibilities in conducting experiments. In order for LSMs to be representative of karst aquifers, a few requirements are introduced: (1) the ability to simulate heterogeneous distributions of karst hydraulic parameters, (2) establish Darcian and non‐Darcian flow regimes and exchange between the matrix and conduits, (3) placement of adequate sampling points and intervals, and (4) achieving some degree of geometric, kinematic, and dynamic similitude to represent field conditions.