bluuebunny/crossref_metadata_2025 huggingface dataset:
Milk coagulation and gastric emptying in women experiencing gastrointestinal symptoms after ingestion of cow's milk
Authors: van Eijnatten Elise J. M. , Camps Guido , Guerville Mathilde , Fogliano Vincenzo , Hettinga Kasper , Smeets Paul A. M.
Published: October 2023

Background

Gastrointestinal symptoms after drinking milk are often attributed to lactose intolerance or cow's milk allergy. However, some individuals without either condition still report gastrointestinal symptoms after drinking milk. This may be caused by gastric emptying (GE) rate or gastric protein coagulation. This study aimed to compare GE rate and protein coagulation after milk consumption between individuals reporting gastrointestinal symptoms and those without symptoms using a novel gastric MRI approach.

Methods

Thirty women were included in this case–control study, of whom 15 reported gastrointestinal symptoms after drinking milk and 15 were controls. Participants underwent gastric MRI before and up to 90 min after consumption of 250 mL cow's milk. Gastric content volume and image texture of the stomach contents were used to determine GE and changes in the degree of coagulation.

Key Results

GE half‐time did not differ between the groups (gastrointestinal symptom group 66 ± 18 min; control group 61 ± 14 min, p = 0.845). The gastrointestinal symptom group reported symptoms from 30 min onwards and rated pain highest at 90 min. The control group reported no symptoms. Image texture analyses showed a significantly higher percentage of coagulum and lower percentage of liquid in the group in the GI symptom group (MD 11%, 95% CI [3.9, 17], p = 0.003). In vitro data suggests that pH and proteolytic enzyme activity influence the coagulum structure.

Conclusions and Inferences

Gastric milk coagulation and emptied fraction of stomach content may differ between individuals experiencing symptoms after milk consumption, possibly due to differences in pH and proteolytic enzyme activity.
From preschool wheezing to asthma: Immunological determinants
Authors: Laubhahn Kristina , Schaub Bianca
Published: October 2023

Asthma represents a chronic respiratory disease affecting millions of children worldwide. The transition from preschool wheezing to school‐age asthma involves a multifaceted interplay of various factors, including immunological aspects in early childhood. These factors include complex cellular interactions among different immune cell subsets, induction of pro‐inflammatory mediators and the molecular impact of environmental factors like allergens or viral infections on the developing immune system. Furthermore, the activation of specific genes and signalling pathways during this early phase plays a pivotal role in the manifestation of symptoms and subsequent development of asthma. Early identification of the propensity or risk for asthma development, for example by allergen sensitisation and viral infections during this critical period, is crucial for understanding the transition from wheeze to asthma. Favourable immune regulation during a critical ‘window of opportunity’ in early childhood can induce persistent changes in immune cell behaviour. In this context, trained immunity, including memory function of innate immune cells, has significant implications for understanding immune responses, potentially shaping long‐term immunological outcomes based on early‐life environmental exposures. Exploration of these underlying immune mechanisms that drive disease progression will provide valuable insights to understand childhood asthma development. This will be instrumental to develop preventive strategies at different stages of disease development for (i) inhibiting progression from wheeze to asthma or (ii) reducing disease severity and (iii) uncovering novel therapeutic strategies and contributing to more tailored and effective treatments for childhood asthma. In the long term, this shall empower healthcare professionals to develop evidence‐based interventions that reduce the burden of asthma for children, families and society overall.
Atypical cutaneous findings of hand‐foot‐mouth disease in children: A systematic review
Authors: Starkey Samantha Y. , Mar Kristie , Khaslavsky Sophie , Seeburruth Darshana , Khalid Bushra , Virmani Divya , Lam Joseph M. , Mukovozov Ilya
Published: October 2023

Introduction

Hand‐foot‐mouth disease (HFMD) is a common childhood infectious disease. Atypical skin findings of HFMD, often associated with coxsackievirus A6 (CVA6), were first reported in 2008, with increasing reports worldwide since. Atypical lesions of HFMD often involve sites beyond the palms and soles and tend to have unusual, polymorphic morphology.

Methods

A systematic review was conducted on clinical features and outcomes of pediatric HFMD with atypical cutaneous manifestations.

Results

Eighty‐five studies were included, representing 1359 cases with mean age 2.4 years and a male predominance of 61%. The most reported morphologies were vesicles (53%), papules (49%), and bullae (36%). Other morphologies included eczema herpeticum‐like (19%), purpuric/petechial (7%), and Gianotti Crosti‐like (4%). Common atypical sites included the arms and/or legs (47%), face (45%), and trunk (27%). CVA6 was identified in 63% of cases. Symptoms resolved in a mean of 10 days. Overall, 16% of cases received treatment, most commonly with acyclovir, intravenous antibiotics, or topical steroids. The most common complications were nail changes (21%) and desquamation (4%) which occurred a mean of 3 and 2 weeks after symptoms, respectively.

Conclusion

Due to unusual morphologies resembling other conditions, HFMD with atypical cutaneous findings may be misdiagnosed, leading to inappropriate and unnecessary investigations, hospitalization, and treatment. Greater awareness of atypical presentations of HFMD is warranted to improve patient care and counseling on infection control precautions.
Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study
Authors: Moudgil Asha , Sgambat Kristen , Benoit Elizabeth , Seifert Michael E. , Bharadwaj Madhumithaa , Jain Amrish , Mansuri Asif , Harshman Lyndsay , Katsoufis Chryso , Somers Michael
Published: October 2023

Background

Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients.

Methods

Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post‐transplant.

Results

The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p = .02), increased number of hospitalizations (82% vs. 67%, p = .01), and viral replications (79% vs. 47%, p < .0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow‐up (−7 vs. −1 mL/min/1.73 m2, p = .05).

Conclusions

Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post‐transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post‐transplant outcomes.
Extracts of Trichocline sinuata (Asteraceae) as natural sensitizers in the photodynamic inactivation of Candida albicans
Authors: Schiavi Paulina Cardoso , Svetaz Laura , Petenatti Elisa , Sortino Maximiliano , Tempesti Tomas C. , Funes Matías
Published: October 2023

Despite significant progress in the development of phototherapy drugs, it is widely recognized that natural products remain the primary source of new photoactive compounds. Exploring uncharted flora in the east‐central region of Argentina may offer a vast array of opportunities to isolate new photoactive molecules or plant extracts with high potential for use in antimicrobial photodynamic therapy (aPDT) against Candida albicans. To assess the photofungicidal potential of T. sinuata (“contrayerba”) against C. albicans, the extracts underwent spectroscopic and chromatographic analysis, resulting in the identification of furanocoumarin metabolites with similar spectrophotometric properties in all extracts. The extract profiles were created using UHPLC‐DAD, and seven furanocoumarins (FCs) were detected. The highest photoinactivation against C. albicans was observed for dicholormethanic extracts (MFC = 62.5 μg/mL), equal to xanthotoxin employed as a positive control. Furthermore, we determine that photochemical mechanisms dependent on oxygen (type I and type II processes) and mechanisms independent of oxygen (photoadduct formation) are involved in the death of these yeasts. These results support the use of native plants of the east‐central region of Argentina as potent sensitizers for aPDT and suggest that they can replace xanthotoxin in treating superficial yeast infections of the skin.
Risk assessment for conventional diesel exhaust (before 1990) and lung cancer in a cohort of miners
Authors: Park Robert M
Published: October 2023

Diesel exhaust in the latter half of the 20th century has been found to be a lung carcinogen. Conventional diesel emissions continue in the transportation, mining, construction, and farming industries. From the Diesel Exhaust in Miners Study, a public‐use dataset was used to calculate the excess lifetime risk of lung cancer associated with diesel exposure (1947–1997). Excess rates of lung cancer mortality associated with respirable elemental carbon (REC) and possible other mining exposures (e.g., oil mists, explosives emissions) were investigated using Poisson regression methods. Lung cancer mortality declined with increasing employment duration while increasing with cumulative REC and non‐diesel exposures, suggesting a strong worker survivor effect. Attenuation of the REC effect was observed with increasing cumulative exposure. After adjustment for employment duration, the excess rate ratio for lung cancer mortality was 0.67 (95% CI = 0.35–0.99) for a 10‐year lagged exposure to 200 μg/m3 REC, a typical below‐ground exposure in the study mines. At exposures of 200, 10, and 1 μg/m3 REC, the estimated excess lifetime risks, respectively, were 119, 43, and 8.7 per thousand. Analysis of an inception cohort hired after dieselization commenced produced smaller and less certain estimates of lifetime risk. From exposures to conventional diesel engine exhaust common in occupational groups in the past, the excess lifetime risk of lung cancer was more than 5%. Ambient REC exposures in the general population were estimated to confer lifetime risks of 0.14 to 14 per thousand, depending on assumptions made.
TBTs, firm organization and labor structure
Authors: Barba Navaretti Giorgio , Fontagné Lionel , Orefice Gianluca , Pica Giovanni , Rosso Anna Cecilia
Published: October 2023

This article investigates the effect of shocks to the occupational structure of exporting firms induced by the introduction of technical barriers to trade (TBTs) in importing countries. We rely on specific trade concerns data to identify trade‐restrictive TBT measures, combined with matched employer‐employee data for French exporters over the period 1995–2010, and information on the product‐destinations served by each exporter. Controlling for time‐invariant firm/occupation fixed effects and for time‐varying sector/occupation shocks, the 2SLS estimates show that exporting firms adapt to the imposition of TBTs at destination by increasing the share of managers at the expense of blue collars, white collars and other professionals.
Everyday sense making and the discursive delineation of social policy space in Zambia
Authors: Wolkenhauer Anna
Published: October 2023

This article connects the notions of policy space and social contract in order to understand the importance of everyday discourse for the perceived legitimacy of social policy choices and emerging responsibilities in Zambia. Based on a Grounded Theory analysis of interview and document material, the article reconstructs common sense ideas about the limited resources of the state, from which modalities in the Social Cash Transfer programme, especially the requirements for targeting and graduation, are derived. It moreover explores how from these limited means also follows the sharing of responsibilities between the state and the recipients themselves, giving way to a self‐responsibility discourse. Thereby, the attempt by implementing officers and the wider community to rationalise distributional choices in light of wide‐spread poverty, shape the social contract between the state and citizens in Zambia and ultimately also delineate the space of what becomes possible to imagine within social policy. The article concludes with an argument for broadening social policy visions away from the individual level towards tackling the underlying structural causes of poverty by connecting social with economic interventions.
Boosting the performance of pretrained CNN architecture on dermoscopic pigmented skin lesion classification
Authors: Nugroho Erwin Setyo , Ardiyanto Igi , Nugroho Hanung Adi
Published: October 2023

Background

Pigmented skin lesions (PSLs) pose medical and esthetic challenges for those affected. PSLs can cause skin cancers, particularly melanoma, which can be life‐threatening. Detecting and treating melanoma early can reduce mortality rates. Dermoscopic imaging offers a noninvasive and cost‐effective technique for examining PSLs. However, the lack of standardized colors, image capture settings, and artifacts makes accurate analysis challenging. Computer‐aided diagnosis (CAD) using deep learning models, such as convolutional neural networks (CNNs), has shown promise by automatically extracting features from medical images. Nevertheless, enhancing the CNN models' performance remains challenging, notably concerning sensitivity.

Materials and methods

In this study, we aim to enhance the classification performance of selected pretrained CNNs. We use the 2019 ISIC dataset, which presents eight disease classes. To achieve this goal, two methods are applied: resolution of the dataset imbalance challenge through augmentation and optimization of the training hyperparameters via Bayesian tuning.

Results

The performance improvement was observed for all tested pretrained CNNs. The Inception‐V3 model achieved the best performance compared to similar results, with an accuracy of 96.40% and an AUC of 0.98.

Conclusion

According to the study, classification performance was significantly enhanced by augmentation and Bayesian hyperparameter tuning.
Conjugacy of transitive SFTs minus periodic points
Authors: Salo Ville
Published: October 2023

It is a question of Hochman whether any two one‐dimensional topologically mixing subshifts of finite type (SFTs) with the same entropy are topologically conjugate when their periodic points are removed. We give a negative answer, and, in fact, we prove the stronger result that there is a canonical correspondence between topological conjugacies of transitive SFTs and topological conjugacies between the systems obtained by removing the periodic points.
Joint integrability and spectral rigidity for Anosov diffeomorphisms
Authors: Gogolev Andrey , Shi Yi
Published: October 2023

Let be an Anosov diffeomorphism whose linearization is irreducible. Assume that is also absolutely partially hyperbolic where a weak stable subbundle is considered as the center subbundle. We show that if the strong stable subbundle and the unstable subbundle are jointly integrable, then is dynamically coherent and all foliations match corresponding linear foliation under the conjugacy to the linearization . Moreover, admits the finest dominated splitting in the weak stable subbundle with dimensions matching those for , and it has spectral rigidity along all these subbundles. In dimension 4, we also obtain a similar result by grouping the weak stable and unstable subbundles together as a center subbundle and assuming joint integrability of the strong stable and unstable subbundles. As an application, we show that for every symplectic diffeomorphism that is ‐close to an irreducible nonconformal automorphism , the extremal subbundles of are jointly integrable if and only if is smoothly conjugate to .
Functional knockout of the TRPV1 channel has no effect on the exercise pressor reflex in rats
Authors: Anselmi Laura , Ducrocq Guillaume P. , Ruiz‐Velasco Victor , Stocker Sean D. , Higgins Shannon P. , Kaufman Marc P.
Published: October 2023

The role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed light on this controversy, we compared the exercise pressor reflex between newly developed TRPV1+/+, TRPV1+/− and TRPV1−/− rats. Carotid arterial injection of capsaicin (0.5 μg), evoked significant pressor responses in TRPV1+/+ and TRPV1+/− rats, but not in TRPV1−/− rats. In acutely isolated dorsal root ganglion neurons innervating the gastrocnemius muscles, capsaicin evoked inward currents in neurons isolated from TRPV1+/+ and TRPV1+/− rats but not in neurons isolated from TRPV1−/− rats. The reflex was evoked by stimulating the tibial nerve in decerebrated rats whose femoral artery was either freely perfused or occluded. We found no difference between the reflex in the three groups of rats regardless of the patency of the femoral artery. For example, the peak pressor responses to contraction in TRPV1+/+, TRPV1+/− and TRPV1−/− rats with patent femoral arteries averaged 17.1 ± 7.2, 18.9 ± 12.4 and 18.4 ± 8.6 mmHg, respectively. Stimulation of the tibial nerve after paralysis with pancuronium had no effect on arterial pressure, findings which indicated that the pressor responses to contraction were not caused by electrical stimulation of afferent tibial nerve axons. We also found that expression levels of acid‐sensing ion channel 1 and endoperoxide 4 receptor in the L4 and 5 dorsal root ganglia were not upregulated in the TRPV1−/− rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex in rats whose contracting muscles have either a patent or an occluded arterial blood supply.

image

Key points

A reflex arising in contracting skeletal muscle contributes to the increases in arterial blood pressure, cardiac output and breathing evoked by exercise.

The sensory arm of the reflex comprises both mechanoreceptors and metaboreceptors, of which the latter signals that blood flow to exercising muscle is not meeting its metabolic demand.

The nature of the channel on the metaboreceptor sensing a mismatch between supply and demand is controversial; some believe that it is the transient receptor potential vanilloid 1 (TRPV1) channel.

Using genetically engineered rats in which the TRPV1 channel is rendered non‐functional, we have shown that it is not needed to evoke the metaboreflex.
Extracellular pH signals affect rat vascular tone by rapid transduction into intracellular pH changes.
Authors: Austin C , Wray S
Published: October 2023

1. Changes in extracellular pH (pHo) are known to produce large effects on vascular tone, but the mechanisms involved are not understood. As changes in intracellular pH (pHi) can also affect vascular tone, we have investigated the effects of changing pHo upon both pHi and tone. 2. Strips of rat mesenteric resistance vessels were loaded with the pH‐sensitive fluorophore SNARF 1; thus tension and pHi could be simultaneously measured as pHo was altered. 3. Whenever pHo was altered there was a corresponding alteration of pHi. Furthermore, when pHo was changed the pHi change was more rapid than that reported to occur in other cells. The time to half‐peak intracellular response was 38 +/‐ 4 s (n = 11). The induced pHi change was also less attenuated than in many other cells studied. Thus a ratio of 0.73 was obtained for the change in pHi per unit pHo change (n = 7). 4. An increase in pHi produced by an increase in pHo was accompanied by an increase in tension in the vascular strips. In other experiments pHi was increased at constant pHo by the addition of the weak base trimethylamine (40 mM). This also elevated tension in the strips. Conversely when pHo was changed while pHi was held at resting values, no change in vascular tone occurred. 5. It is concluded that the effects of pHo on vascular tone are due to the induced change in intracellular pH, and that the vascular smooth muscle cell is functionally well adapted to respond to changes in tissue pH, thereby allowing blood flow to a tissue to be rapidly altered to meet changing needs.
Kinetic analysis of two types of Na+ channels in rat dorsal root ganglia.
Authors: Ogata N , Tatebayashi H
Published: October 2023

1. The gating properties of two types of Na+ channels were studied in neurones isolated from rat dorsal root ganglia using the whole cell variation of the patch electrode voltage‐clamp technique. 2. Two types of Na+ currents (INa) were identified on the basis of their sensitivity to tetrodotoxin (TTX). One type was insensitive to TTX (up to 0.1 mM), while the other type was blocked by 1 nM of TTX. Whereas they were both insensitive to 50 microM Cd2+, a high concentration (2 mM) of Co2+ selectively inhibited the TTX‐insensitive type. 3. The activation thresholds were about ‐60 and ‐40 mV for the TTX‐sensitive and the TTX‐insensitive INa, respectively. Activation of the TTX‐sensitive INa developed with a sigmoidal time course which was described by m3 kinetics, whereas the activation of the TTX‐insensitive INa was described by a single exponential function. A deactivation process, as measured by the tail current upon repolarization, followed an exponential decay in either type of INa. 4. The rate constant of activation indicated that under comparable membrane potential conditions, the TTX‐insensitive channels open 4‐5 times slower than the TTX‐sensitive ones upon depolarization. Likewise, the rate constant of inactivation indicated that the TTX‐insensitive channels inactivate 3‐7 times more slowly than the TTX‐sensitive ones upon repolarization. 5. The steady‐state activation curve for the TTX‐insensitive INa was shifted about 20 mV in the positive direction from that for the TTX‐sensitive INa. 6. The steady‐state inactivation curve for the TTX‐insensitive INa as obtained with a 0.5 s prepulse was shifted about 26 mV in the positive direction from that for the TTX‐sensitive INa, indicating a greater availability for the TTX‐insensitive INa in depolarized membrane. However, on increasing the duration of prepulse, the inactivation curve for the TTX‐insensitive INa, but not for the TTX‐sensitive INa, shifted in the negative direction due to an extremely slow inactivation process in the TTX‐insensitive INa. Consequently, an overlap between the activation and inactivation curves which causes a steady influx of Na+ (window current) became progressively reduce. 7. The time course of INa decay was best described by a single exponential process in either the TTX‐sensitive or TTX‐insensitive INa, whereas the development of inactivation and the recovery from inactivation, which were measured by a conventional double‐pulse protocol, followed a second order process in either channel type.(ABSTRACT TRUNCATED AT 400 WORDS)
Light‐induced currents in Xenopus oocytes expressing bovine rhodopsin.
Authors: Knox B E , Khorana H G , Nasi E
Published: October 2023

1. We have investigated the functioning of bovine rod opsin, which is efficiently synthesized from RNA made by in vitro transcription, following injection into Xenopus oocytes. We found that oocytes expressing the gene for opsin exhibit light‐dependent ionic currents only after pigment generation by incubation with 11‐cis‐retinal. These currents are similar to the endogenous muscarinic acetylcholine (ACh) response of oocytes, but their amplitude is substantially smaller. 2. In order to optimize the conditions for obtaining light‐induced currents in RNA‐injected oocytes, the native ACh response was examined under several conditions. It was found that elevated external calcium markedly enhances the muscarinic response and that these currents have a non‐linear dependence on membrane voltage, increasing substantially with depolarization. 3. Using the optimal conditions for evoking the largest ACh responses, (28 mM [Ca2+]o, 0 mV, omission of serum and Hepes from the media), the light‐evoked currents obtained in RNA‐injected oocytes were remarkably enhanced, and responses to multiple light stimuli could be obtained. 4. The light response appeared to desensitize, even after long periods of recovery and pigment regeneration. By contrast, the ACh responses continued to appear normal. These results suggest that desensitization of photoresponses expressed in Xenopus oocytes involve changes at early stages of the pathway, resulting in a reduced ability of rhodopsin to couple to the endogenous signalling system.
Properties of stretch‐activated channels in myocytes from the guinea‐pig urinary bladder.
Authors: Wellner M C , Isenberg G
Published: October 2023

1. Stretch‐activated channels (SACs) were analysed on patches attached to myocytes isolated from the guinea‐pig urinary bladder. At 22 degrees C application of ‐2 to ‐4 kPa to the patch electrode induced SACs at a density of one to two per patch (3‐5 M omega electrodes). 2. With electrodes containing 145 mM K+, 20 mM TEA and 2 mM Mg2+, the single channel current followed a linear I‐V curve with a slope conductance of 39 +/‐ 5 pS (mean +/‐ S.D.) and a reversal potential of 2 +/‐ 6 mV. Substitution of chloride by aspartate ions left both parameters unchanged suggesting that the anions do not contribute to the currents. 3. Hyperpolarization from ‐30 to ‐80 mV did not open channels by itself but increased channel activity (NPo; where N is the number of channels in the patch and Po is the probability of the channel being open) twofold. The hyperpolarization‐induced increase in NPo can be attributed to a reduction of long closures. At positive patch potentials numerous blank records strongly diminished NPo. 4. Inward currents through SACs can be carried by a variety of cations. In the presence of 2 mM Mg2+, the respective channel conductance was 40 +/‐ 4 pS for 140 mM K+ > 34 +/‐ 2 pS for 140 mM Na+ > or = 33 +/‐ 6 pS for 140 mM Cs+ > 19 +/‐ 2 pS for 110 mM Ba2+ > 17 +/‐ 2 pS for 110 mM Ca2+. 5. Reduction of CaCl2 from 110 to 10 mM did not change the conductance but shifted the reversal potential from +7 to ‐7 mV; the reversal potentials suggest that SACs are slightly more permeable for Ca2+ than for K+. 6. In the absence of divalent cations, the conductance of K+ was 82 +/‐ 4 pS for inward but 45 pS for outward currents. Addition of either 2 mM Ca2+ or 2 mM Mg2+ reduced the conductance for inward currents to 40 pS. 7. The change from 140 to 14 mM KCl plus 136 mM Tris‐Cl reduced the conductance from 82 to 56 pS whereas the reversal potential shifted only from ‐4 to ‐9 mV. When 20 mM K+ and 300 mM sucrose were applied, the conductance fell to 39 pS and the reversal potential shifted by ‐30 mV. The results suggest that Tris+ can permeate through SACs when extracellular divalent cations are absent.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of lanthanum at snake twitch and tonic muscle fibre endplates.
Authors: Coniglio L M , Hendricks G M , Parsons R L
Published: October 2023

1. The effects of 1 mM lanthanum on miniature endplate current (MEPC) frequency, amplitude, and decay time course were studied in voltage‐clamped twitch and tonic muscle fibres in the garter snake, Thamnophis. 2. Lanthanum produced a marked increase in MEPC frequency in both fibre types. The maximum frequency in lanthanum was greater at twitch endplates than at tonic endplates although the increase in frequency relative to control levels was as great in tonic fibres as in twitch fibres. 3. In twitch fibres continually exposure to lanthanum, the frequency of MEPCs reached a peak value and then declined progressively until, after approximately 6 h, no MEPCs were recorded. In contrast, at tonic endplates exposed to 1 mM lanthanum, MEPC frequency remained elevated above control levels for periods greater than 20 h. 4. Lanthanum decreased the mean amplitude of MEPCs, skewed the amplitude distribution and increased MEPC duration at both twitch and tonic fibre endplates. 5. Ultrastructural analysis showed that after a 15 min exposure to 1 mM lanthanum, approximately half of the boutons innervating a twitch fibre contained fewer synaptic vesicles than boutons at control endplates, whereas nerve terminals innervating tonic fibre endplates were similar in appearance to those in control preparations. At endplates on both fibres, the postsynaptic membrane was more electron dense than that of control preparations. 6. Following a 6 h exposure to lanthanum, all nerve terminals innervating twitch endplates contained only a few synaptic vesicles and numerous intracellular deposits of electron dense material. The nerve terminals innervating tonic endplates still contained many synaptic vesicles, but the number appeared to be less than that of tonic terminals in untreated preparations. 7. The results demonstrate that lanthanum stimulates spontaneous quantal transmitter release from nerve terminals innervating either twitch or tonic fibres. However, the terminals innervating twitch fibres become depleted of synaptic vesicles, whereas this does not occur as readily in nerve terminals innervating tonic fibres.
Silent period evoked by transcranial stimulation of the human cortex and cervicomedullary junction.
Authors: Inghilleri M , Berardelli A , Cruccu G , Manfredi M
Published: October 2023

1. The silent period evoked in the first dorsal interosseous (FDI) muscle after electrical and magnetic transcranial stimulation (TCS), electrical stimulation of the cervicomedullary junction and ulnar nerve stimulation was studied in ten healthy subjects. 2. With maximum‐intensity shocks, the average duration of the silent period was 200 ms after electrical TCS, 300 ms after magnetic TCS, 43 ms after stimulation at the cervicomedullary junction and 100 ms after peripheral nerve stimulation. 3. The duration of the silent period, the amplitude of the motor‐evoked potential, and the twitch force produced in the muscle were compared at increasing intensities of magnetic TCS. When the stimulus strength was increased from 30 to 70% of the stimulator output, the duration of the silent period lengthened as the amplitude of the motor potential and force of the muscle twitch increased. At 70 to 100% of the output, the amplitude of the motor potential and force of the muscle twitch saturated, whereas the duration of the silent period continued to increase. 4. Proximal arm muscle twitches induced by direct electrical stimulation of the biceps and extensor wrist muscles produced no inhibition of voluntary activity in the contracting FDI muscle. 5. The level of background activation had no effect on the duration of the silent period recorded in the FDI muscle after magnetic TCS. 6. Corticomotoneurone excitability after TCS was studied by means of a single magnetic conditioning shock and a test stimulus consisting either of one single magnetic shock or single and double electrical shocks (interstimulus interval 1.8 ms) in the relaxed muscle. A conditioning magnetic shock completely suppressed the response evoked by a second magnetic shock, reduced the size of the response evoked by a single electrical shock but did not affect the response evoked by double electrical shocks. Inhibition of the test magnetic shock was also present during muscle contraction. 7. Our findings indicate that the first 50 ms of the silent period after TCS are produced mainly by spinal mechanisms such as after‐hyperpolarization and recurrent inhibition of the spinal motoneurones. If descending inhibitory fibres contribute, their contribution is small. Changes in proprioceptive input probably have a minor influence. From 50 ms onwards the silent period is produced mainly by cortical inhibitory mechanisms.
The influence of intracellular pH on contraction, relaxation and [Ca2+]i in intact single fibres from mouse muscle.
Authors: Westerblad H , Allen D G
Published: October 2023

1. The effects of intracellular pH (pHi) on myoplasmic free calcium concentration ([Ca2+]i) and contractile performance were studied in intact single fibres dissected from mouse skeletal muscle. Indo‐1 was used to measure [Ca2+]i and pHi was altered by changing perfusate CO2. 2. Tetanic tension was decreased at acidic pHi and increased at alkaline pHi whereas the rate of mechanical relaxation was showed at both acidic and alkaline pHi. Resting and tetanic [Ca2+]i were increased at acidic pHi and decreased at alkaline pHi while the final rate of decline of [Ca2+]i after a tetanus was markedly slowed at acid pHi but only marginally accelerated at alkaline pHi. 3. Steady‐state [Ca2+]i‐tension curves were constructed from measurements of tetani at different stimulus frequencies. The curves at acid pHi showed a reduced maximum Ca(2+)‐activated tension and a reduced Ca2+ sensitivity, and curves at alkaline pHi showed the opposite changes. 4. Two methods were devised to determine the contribution of [Ca2+]i to the rate of relaxation. In one method the instantaneous tension was plotted as a function of instantaneous [Ca2+]i throughout a tetanus and compared with the steady‐state [Ca2+]i‐tension relation. In a second method the [Ca2+]i signal during a tetanus was converted to a Ca(2+)‐derived tension record by means of the steady‐state [Ca2+]i‐tension relation and this Ca(2+)‐derived tension was then compared to the true tension. 5. The sarcoplasmic reticulum (SR) pump function was analysed by plotting ‐d[Ca2+]i/dt against [Ca2+]i during the final slow decline of [Ca2+]i after a tetanus. This analysis shows that the Ca2+ uptake by the SR is a third‐ or fourth‐power function of [Ca2+]i and that acidosis substantially slows the rate of SR Ca2+ pumping. 6. In conclusion, the slowing of relaxation at acidic pHi could be attributed to a slowing of cross‐bridge detachment rather than the observed slowing of the rate of uptake of Ca2+. Conversely the slowing of relaxation in alkaline pHi could be attributed to the increase of Ca2+ sensitivity of the myofibrillar proteins.
Modification of the adenosine 5'‐triphosphate‐sensitive K+ channel by trypsin in guinea‐pig ventricular myocytes.
Authors: Furukawa T , Fan Z , Sawanobori T , Hiraoka M
Published: October 2023

1. The adenosine 5'‐triphosphate (ATP)‐sensitive K+ channel current was recorded in guinea‐pig ventricular myocytes using the patch clamp technique with inside‐out patch configuration. Modification of the channel activity by intracellular application of an endoprotease trypsin was studied, and was related to a possible model of regulation of this channel. 2. Maximal ATP‐sensitive K+ channel activity was observed immediately upon formation of inside‐out patches in the ATP‐free internal solution, thereafter activity declined both spontaneously and gradually with time; a phenomenon known as rundown. When trypsin (1 mg/ml) was applied to the intracellular side of the membrane upon formation of inside‐out patches, spontaneous run‐down did not occur, and this trypsin action was irreversible. Neither trypsin (1 mg/ml) applied with trypsin inhibitor (0.25 mg/ml) nor heat‐denatured trypsin (1 mg/ml) could mimic this effect. When trypsin was applied to the patches after run‐down, channels were reactivated at approximately 13 min. 3. Treatment with trypsin did not affect unitary current amplitude, channel gating kinetics, or sensitivity to intracellular ATP. 4. Intracellularly applied Ca2+ induced run‐down of channel activity in a dose‐dependent manner. In membrane patches that were treated with trypsin (1 mg/ml) for 20 min, intracellularly applied Ca2+ up to 1 mM did not induce run‐down of channel activity. 5. Intracellular application of an exopeptidase, carboxypeptidase A (1 mg/ml), but not Leu‐aminopeptidase (0.5 mg/ml), prevented spontaneous or Ca(2+)‐induced run‐down of channel activity. 6. As postulated for several other channels, such as Na+ and Ca2+ channels, there may be a possible ‘chemical gate’ that is responsible for run‐down of this channel activity. Application of trypsin might somehow modify this ‘chemical gate’, resulting in prevention of spontaneous or Ca(2+)‐induced run‐down. This target site for trypsin may be situated on the carboxy‐terminus of the channel proteins, or of associated regulatory units. Because ATP sensitivity remained intact after trypsin treatment, the trypsin‐selective site for channel inhibition is not related physically to the ATP binding site.
La determinación social del proceso salud-enfermedad en el contexto latinoamericano: la aportación de Oliva López-Arellano
Authors: Correia Daniele , Mendes Áquilas , Carnut Leonardo
Published: October 2023

El objetivo de este artículo es investigar la producción científica del pensamiento de Oliva López-Arellano, para verificar su contribución al enfoque de la determinación social del proceso salud-enfermedad en el modo de producción capitalista. Para ello, se realizó una revisión crítica de su producción a través de tres repositorios de estudios científicos, dos en los portales de la Biblioteca Virtual de Salud (BVS) y PubMed, y uno en una base de datos directa, la Scientific Electronic Library Online (Scielo). Tras los procesos de selección, se eligieron 14 artículos que fueron discutidos en base a dos dimensiones que facilitan la construcción del pensamiento de la autora: i) enfoque sobre la determinación social del proceso salud-enfermedad; ii) enfoque sobre la relación con el modo de producción capitalista. De manera específica, se apreció en la producción científica de López-Arellano algunas discusiones sintetizadas en cuatro categorías de análisis: ‘trabajo’, ‘pensamiento sanitario latinoamericano’, ‘Estado y economía política’, ‘necesidades de salud’. Con las evidencias encontradas, se pudo concluir que la producción de López-Arellano contribuye a la realización de una aproximación crítica al contexto sanitario y su relación con el modo de producción capitalista, aunque no utilice explícitamente la Teoría Social de Marx en sus aportaciones teóricas. Es una contribución fundamental para indicar los desafíos para el campo de la salud colectiva/medicina social en América Latina, posibilitando pensar la salud en el contexto del capitalismo contemporáneo. Palabras clave: determinación social de la salud, pensamiento, capitalismo, América Latina.
Perspectivas de la incapacidad temporal en Colombia: aspectos clínicos, legales, operativos y económicos
Authors: Galindo-Buitrago José Israel , Valero-Pacheco Ivonne Constanza , Rodríguez Páez Fredy Guillermo , Riaño Casallas Martha Isabel
Published: October 2023

Objetivo: Comprender los problemas asociados a la incapacidad temporal (IT) en Colombia en particular aspectos clínicos, legales, operativos y económicos, y sus implicaciones para el sistema de salud y de riesgos laborales. Materiales y métodos: Estudio de tipo cualitativo con enfoque social, investigación participativa, en el cual se utiliza como técnica para la recolección de información los paneles de expertos, que conlleven a una definición de categorías. con lo encontrado entre nuestros expertos y la literatura existente. Posterior a esto, los investigadores emiten unas conclusiones de los hallazgos encontrados. Resultados: Se realiza análisis de la información emitida por los expertos, se definen categorías y códigos, las categorías concebidas para el estudio fueron: i) El diagnóstico (enfermedad o lesión), ii) Duración de la incapacidad temporal, iii) Gestión económica de las incapacidades (por parte de las entidades que les corresponde), iv) Gestión Clínica de las incapacidades, v) Factores socioeconómicos, vi) Factores normativos (legales), vii) Posiciones/perspectivas de los actores involucrados e implicaciones para el Sistema de Seguridad Social, y viii) Metodología para estimar el costo de la incapacidad temporal. Conclusión: Teniendo en cuenta la problemática que generan las IT en Colombia se debe establecer de forma clara a todos los actores, qué orígenes tienen las incapacidades, cómo se dictamina desde el ámbito clínico, legal y operativo, en razón a que el país necesita minimizar la ineficiencia y el desperdicio en salud generado por las incapacidades temporales, fenómenos que son evitables y precisan de un esfuerzo mancomunado intersectorial para su abordaje.
Using long-range transmissions in the Beaufort Gyre to test the sound-speed equation at high pressure and low temperature
Authors: Vazquez Heriberto J. , Cornuelle Bruce D. , Worcester Peter F. , Dzieciuch Matthew A. , Colosi John A. , Nash Jonathan D.
Published: October 2023

An ocean acoustic tomography array with a radius of 150 km was deployed in the central Beaufort Gyre during 2016–2017 for the Canada Basin Acoustic Propagation Experiment. Five 250-Hz transceivers were deployed in a pentagon, with a sixth transceiver at the center. A long vertical receiving array was located northwest of the central mooring. Travel-time anomalies for refracted-surface-reflected acoustic ray paths were calculated relative to travel times computed for a range-dependent sound-speed field from in situ temperature and salinity observations. Travel-time inversions for the three-dimensional sound-speed field consistent with the uncertainties in travel time [∼2 ms root mean square (rms)], receiver and source positions (∼ 3 m rms), and sound speed calculated from conductivity-temperature-depth casts could not be obtained without introducing a deep sound-speed bias (below 1000 m). Because of the precise nature of the travel-time observations with low mesoscale and internal wave variability, the conclusion is that the internationally accepted sound-speed equation (TEOS-10) gives values at high pressure (greater than 1000 m) and low temperature (less than 0 °C) that are too high by 0.14–0.16 m s−1.
Global distribution and evolutionary transitions of floral symmetry in angiosperms
Authors: Wang Yunyun , Luo Ao , Lyu Tong , Dimitrov Dimitar , Liu Yunpeng , Li Yichao , Xu Xiaoting , Freckleton Robert P , Hao Zhanqing , Wang Zhiheng
Published: October 2023

Floral symmetry plays an important role in plant-pollinator interactions and may have remarkable impacts on angiosperm diversification. However, spatiotemporal patterns in floral symmetry and drivers of these patterns remain unknown. Here, using newly compiled floral symmetry (actinomorphy versus zygomorphy) data of 279,877 angiosperm species and their distributions and phylogenies, we estimated global geographic patterns and macroevolutionary dynamics of floral symmetry. We found that frequency of actinomorphic species increased with latitude, while that of zygomorphic species decreased. Solar radiation, present-day temperature, and Quaternary temperature change correlated with geographic variation in floral symmetry frequency. Evolutionary transitions from actinomorphy to zygomorphy dominated floral symmetry evolution, although the transition rate decreased with decreasing paleotemperature throughout the Cenozoic. Notably, we found that zygomorphy may not favor diversification of angiosperms as previously observed in some clades. Our study demonstrates the influence of (paleo)climate on spatiotemporal patterns in floral symmetry and challenges previous views about role of flower symmetry in angiosperm diversification.
Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions
Authors: Hildenbrand Karen , Bohnacker Sina , Menon Priyanka Rajeev , Kerle Anna , Prodjinotho Ulrich F. , Hartung Franziska , Strasser Patrick C. , Catici Dragana A. M. , Rührnößl Florian , Haslbeck Martin , Schumann Kathrin , Müller Stephanie I. , da Costa Clarissa Prazeres , Esser-von Bieren Julia , Feige Matthias J.
Published: October 2023

Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each family member consists of an α and a β subunit that together form a composite cytokine. Within the IL-12 family, IL-35 remains particularly ill-characterized on a molecular level despite its key role in autoimmune diseases and cancer. Here we show that both IL-35 subunits, IL-12α and EBI3, mutually promote their secretion from cells but are not necessarily secreted as a heterodimer. Our data demonstrate that IL-12α and EBI3 are stable proteins in isolation that act as anti-inflammatory molecules. Both reduce secretion of proinflammatory cytokines and induce the development of regulatory T cells. Together, our study reveals IL-12α and EBI3, the subunits of IL-35, to be functionally active anti-inflammatory immune molecules on their own. This extends our understanding of the human cytokine repertoire as a basis for immunotherapeutic approaches.
Emergence of the Central Atlantic Niño
Authors: Zhang Lei , Wang Chunzai , Han Weiqing , McPhaden Michael J. , Hu Aixue , Xing Wen
Published: October 2023

The Atlantic Niño is characterized by sea surface warming in the equatorial Atlantic, which can trigger La Niña, the cold phase of El Niño–Southern Oscillation (ENSO). Although observations show that the Atlantic Niño has weakened by approximately 30% since the 1970s, its remote influence on ENSO remains strong. Here, we show that this apparent discrepancy is due to the existence of two types of Atlantic Niño with distinct patterns and climatic impacts, which we refer to as the central and eastern Atlantic Niño. Our results show that with equal strength, the central Atlantic Niño has a stronger influence on tropical climate than its eastern counterpart. Meanwhile, the eastern Atlantic Niño has weakened by approximately 50% in recent decades, allowing the central Atlantic Niño to emerge and dominate the remote impact on ENSO. Given the distinct climatic impacts of the two types, it is necessary to distinguish between them and investigate their behaviors and influences on climate in future studies.
Structure of a diatom photosystem II supercomplex containing a member of Lhcx family and dimeric FCPII
Authors: Feng Yue , Li Zhenhua , Li Xiaoyi , Shen Lili , Liu Xueyang , Zhou Cuicui , Zhang Jinyang , Sang Min , Han Guangye , Yang Wenqiang , Kuang Tingyun , Wang Wenda , Shen Jian-Ren
Published: October 2023

Diatoms rely on fucoxanthin chlorophyll
a/c
-binding proteins (FCPs) for their great success in oceans, which have a great diversity in their pigment, protein compositions, and subunit organizations. We report a unique structure of photosystem II (PSII)–FCPII supercomplex from
Thalassiosira pseudonana
at 2.68-Å resolution by cryo–electron microscopy. FCPIIs within this PSII-FCPII supercomplex exist in dimers and monomers, and a homodimer and a heterodimer were found to bind to a PSII core. The FCPII homodimer is formed by Lhcf7 and associates with PSII through an Lhcx family antenna Lhcx6_1, whereas the heterodimer is formed by Lhcf6 and Lhcf11 and connects to the core together with an Lhcf5 monomer through Lhca2 monomer. An extended pigment network consisting of diatoxanthins, diadinoxanthins, fucoxanthins, and chlorophylls
a/c
is revealed, which functions in efficient light harvesting, energy transfer, and dissipation. These results provide a structural basis for revealing the energy transfer and dissipation mechanisms and also for the structural diversity of FCP antennas in diatoms.