bluuebunny/crossref_metadata_2025 huggingface dataset:
Ca(2+)‐dependent block and potentiation of L‐type calcium current in guinea‐pig ventricular myocytes.
Authors: Bates S E , Gurney A M
Published: October 2023

1. The caged calcium compound nitr‐5 has been used to investigate the response of the L‐type calcium current (ICa) of guinea‐pig ventricular cells to a rapid increase in the free intracellular calcium concentration ([Ca2+]i). 2. When 2 mM nitr‐5 or 3 mM DM‐nitrophen was loaded into cells via a patch pipette and photolysed during the decay phase of ICa, a partial block of the current developed within 75 ms. The block was reduced by increasing the pre‐flash [Ca2+]i and enhanced by adding high concentrations of Ca2+ chelators to the pipette‐filling solution. 3. The photolysis‐induced block was not suppressed in the presence of isoprenaline, suggesting a direct action of Ca2+ on the channels rather than a mechanism involving channel phosphorylation. 4. The most prominent effect of nitr‐5 photolysis was a slow potentiation of ICa. When ICa was activated at frequencies between 0.05 and 0.7 Hz with various levels of pre‐flash [Ca2+]i, peak ICa was approximately doubled in amplitude following photolysis. 5. At a stimulation frequency of 0.05 Hz, when nitr‐5 was the only chelator present in the pipette, the time course of the potentiation was fitted by a single exponential with a time constant (tau P) of 2.7 min. When 1 mM CaCl2 was added to the pipette‐filling solution, the time course of the potentiation was slowed (tau P = 6 min), although its amplitude was unchanged. With 12 mM BAPTA (a calcium chelator) added instead of CaCl2, the response was accelerated (tau P = 1.7 min). 6. Equimolar substitution of extracellular Ca2+ with Ba2+ significantly suppressed the flash‐induced potentiation. The time course of the potentiation of the barium current, IBa (tau P = 1.9 min) was similar to that of ICa with BAPTA in the pipette. Potentiation of IBa was largely blocked in Ca(2+)‐depleted cells when CaCl2 was omitted from the pipette. 7. When ICa was activated at frequencies of > or = 0.1 Hz, with 1 mM CaCl2 added to the nitr‐5 (2 mM) in the pipette, the onset of the flash‐induced potentiation was best fitted by two exponentials; one was similar to the single component seen at 0.05 Hz and the other was approximately one order of magnitude faster. The contribution of the faster component was positively correlated to the stimulation frequency. 8. The flash‐induced potentiation of ICa was suppressed in the presence of a supramaximal concentration of the beta‐adrenergic agonist isoprenaline.(ABSTRACT TRUNCATED AT 400 WORDS)
The mechanism of ion transport by the Na(+)‐Ca2+,K+ exchange in rods isolated from the salamander retina.
Authors: Perry R J , McNaughton P A
Published: October 2023

1. Membrane currents caused by the operation of electrogenic Na(+)‐Ca2+,K+ exchange were recorded from isolated rod outer segments under voltage‐clamp using a whole‐cell electrode. 2. Reversed mode exchange currents (Na+i‐Ca2+o,K+o) were recorded with a high internal [Na+] and when both Ca2+ and K+ were present in the external solution. Omission of either Ca2+ or K+ completely suppressed both the reversed exchange current and the entry of Ca2+. 3. The charge transferred by the exchange per Ca2+ ion transported was identical in both forward and reversed modes. 4. The reversed exchange current declined as Ca2+ accumulated inside the outer segment, and the form of this decline was consistent with a first‐order inhibition by internal Ca2+. 5. The reversed exchange current was increased e‐fold by a 230 mV depolarization over the range ‐51 to +29 mV. 6. The activation of reversed exchange by external Ca2+ was well described by first‐order kinetics with a Michaelis constant, KappCao, of 34 microM in the presence of 20 mM external K+. KappCao was reduced by lowering external [K+], was increased by adding external Na+ and was unaffected by membrane potential. 7. External K+ also activated the exchange in a first‐order manner with a Michaelis constant, KappKo, of 151 microM in the presence of 0.5 mM external Ca2+. KappKo was reduced by lowering external [Ca2+], increased by adding external Na+ and was unaffected by membrane potential. 8. When the level of internal Ca2+ was increased via reversed exchange, KappCao diminished in proportion to the reduction in the maximum current, but KappKo remained approximately constant. 9. These observations cannot be reconciled with simple models of the exchange in which ions bind simultaneously at opposite faces of the membrane before transport occurs. The results are broadly consistent with a consecutive model of the exchange in which unbinding of Na+ at either the external or the internal membrane surface is followed by binding of Ca2+ and then K+, and are fully reproduced by a model in which Ca2+ binds before all of the Na+ has dissociated from the exchange molecule.
The mechanism by which cytoplasmic protons inhibit the sodium‐calcium exchanger in guinea‐pig heart cells.
Authors: Doering A E , Lederer W J
Published: October 2023

1. We recorded cardiac sodium‐calcium exchange current (INa‐Ca) in giant excised membrane patches obtained from cardiac myocytes of the adult guinea‐pig. 2. Rapid changes in ion concentrations on the cytoplasmic side of the excised membrane patch were produced using a modified oil‐gate bath. 3. Sodium‐calcium exchange current was activated by step increases in sodium concentration on the cytoplasmic side of the membrane ([Na+]i), which led to an increase in outward INa‐Ca to a new steady‐state level. The [Na+]i required to half‐maximally activate the sodium‐calcium exchange current (K1/2) was 21 mM. 4. Step increases in cytoplasmic calcium concentration ([Ca2+]i) stimulated the [Na+]i‐activated INa‐Ca up to 1 microM [Ca2+]i, then inhibited the exchange current at very high [Ca2+]i (1 mM). 5. A step decrease in cytoplasmic pH from 7.2 to 6.4 (increase in [H+]i) produced a biphasic but monotonic decrease in INa‐Ca. Alkalinization of cytoplasmic pH from 7.2 to 8.0 caused a large, biphasic increase in INa‐Ca. 6. When INa‐Ca was activated by a step increase in [Na+]i and [H+]i was simultaneously increased, the outward current rose to a peak and then declined to a low steady level. The peak current seen was always less than the maximum current produced by an identical elevation of [Na+]i at constant pHi. This reduction in peak outward current reflected a rapid ‘primary’ inhibition of the sodium‐calcium exchange by protons. The decay of the sodium‐calcium exchange current following the peak was slow and corresponded to the time course of the onset of a 'secondary’ proton block. 7. Rapid primary inhibition of the sodium‐calcium exchanger could also be produced by cytoplasmic acidification in the absence of cytoplasmic sodium. The primary blockade was revealed when a subsequent increase in [Na+]i activated INa‐Ca and a smaller peak outward current was observed. Secondary inhibition of the sodium‐calcium exchanger was not, however, produced by cytoplasmic acidification in the absence of cytoplasmic sodium. Regardless of the duration of exposure to elevated [H+]i, the 'secondary’ block by protons was still seen on activation of INa‐Ca by increased [Na+]i as a gradual reduction of outward current amplitude. 8. Treatment of the sodium‐calcium exchanger with the proteolytic enzyme alpha‐chymotrypsin largely removed its sensitivity to protons. 9. We conclude that the action of alpha‐chymotrypsin on the monomeric sodium‐calcium exchange protein is in part to remove a proton‐sensitive regulatory component(s) or render the regulation ineffective.(ABSTRACT TRUNCATED AT 400 WORDS)
Loss of Na+ channel inactivation by anemone toxin (ATX II) mimics the myotonic state in hyperkalaemic periodic paralysis.
Authors: Cannon S C , Corey D P
Published: October 2023

1. Mutations that impair inactivation of the sodium channel in skeletal muscle have recently been postulated to cause several heritable forms of myotonia in man. A peptide toxin from Anemonia sulcata (ATX II) selectively disrupts the inactivation mechanism of sodium channels in a way that mimics these mutations. We applied ATX II to rat skeletal muscle to test the hypothesis that myotonia is inducible by altered sodium channel function. 2. Single‐channel sodium currents were measured in blebs of surface membrane that arose from the mechanically disrupted fibres. ATX II impaired inactivation as demonstrated by persistent reopenings of sodium channels at strongly depolarized test potentials. A channel failed to inactivate, however, in only a small proportion of the depolarizing steps. With micromolar amounts of ATX II, the ensemble average open probability at the steady state was 0.01‐0.02. 3. Ten micromolar ATX II slowed the relaxation of tension after a single twitch by an order of magnitude. Delayed relaxation is the in vitro analogue of the stiffness experienced by patients with myotonia. However, peak twitch force was not affected within the range of 0‐10 microM ATX II. 4. Intracellular injection of a long‐duration, constant current pulse elicited a train of action potentials in ATX II‐treated fibres. After‐depolarizations and repetitive firing often persisted beyond the duration of the stimulus. Trains of action potentials varied spontaneously in amplitude and firing frequency in a similar way to the electromyogram of a myotonic muscle. Both the after‐depolarization and the post‐stimulus firing were abolished by detubulating the fibres with glycerol. 5. We conclude that a loss of sodium channel inactivation alone, without changes in resting membrane conductance, is sufficient to produce the electrical and mechanical features of myotonia. Furthermore, in support of previous studies on myotonic muscle from patients, this model provides direct evidence that only a small proportion of sodium channels needs to function abnormally to cause myotonia.
Changes in NAD(P)H fluorescence and membrane current produced by glutamate uptake into salamander Müller cells.
Authors: Barbour B , Magnus C , Szatkowski M , Gray P T , Attwell D
Published: October 2023

1. Glutamate uptake into isolated, whole‐cell patch‐clamped glial cells was studied by monitoring the increase of cell fluorescence generated as glutamate and NAD(P) were converted into alpha‐ketoglutarate and NAD(P)H by glutamate dehydrogenase. The current generated by the glutamate uptake carrier was recorded simultaneously. 2. L‐Glutamate evoked an increase of cell fluorescence and an inward uptake current. L‐ and D‐aspartate generated an uptake current but no fluorescence response, consistent with the amino acid specificity of glutamate dehydrogenase. 3. In the absence of external sodium the glutamate‐evoked fluorescence response and uptake current were abolished, showing that there is no sodium‐independent glutamate uptake across the cell membrane. 4. Varying the glutamate concentration altered both the fluorescence response and the uptake current. The fluorescence response saturated at a lower glutamate concentration than the uptake current, and depended in a Michaelis‐Menten fashion on the uptake current. 5. The fluorescence response and the uptake current were reduced by membrane depolarization, and also by removal of intracellular potassium. 6. The dependence of the fluorescence response on uptake current when membrane potential was altered or intracellular potassium was removed was the same as that seen when the external glutamate concentration was altered. 7. These fluorescence studies show that glutamate uptake is inhibited by depolarization and by removal of intracellular potassium, consistent with the conclusion of earlier work in which uptake was monitored solely as a membrane current. The data are consistent with high‐affinity electrogenic sodium‐ and potassium‐dependent glutamate uptake with fixed stoichiometry being the only significant influx route for glutamate. Other possible interpretations of the data are also discussed.
Ion permeation through the L‐type Ca2+ channel in rat phaeochromocytoma cells: two sets of ion binding sites in the pore.
Authors: Kuo C C , Hess P
Published: October 2023

1. Both inward and outward unitary Li+ currents through the L‐type Ca2+ channel and discrete block of such currents by either internal or external Ca2+ are recorded. Detailed kinetic analyses are obtained for all of the four experimental configurations (internal or external Ca2+ block of either inward or outward Li+ currents). 2. No matter from which side the blocking Ca2+ ion comes, the exit (unblocking) rates are always the same at the same potential in the same direction of Li+ current flow. This indicates that the high‐affinity Ca2+ binding site (the blocking site) is in the pore, and internal and external Ca2+ both go to the same site to produce the block. In other words, there can only be one high‐affinity Ca2+ binding site or one set of such sites (sites separated by insignificant barriers) in the pore. Furthermore, the direction of exit of the blocking Ca2+ ion is always with, not against, the Li+ current flow. This suggests ion‐ion interaction (the ‘long pore effect’) in the high‐affinity sites. Therefore there must be more than one high‐affinity site in the pore. Overall it is concluded that the pore must contain a set of high‐affinity Ca2+ binding sites separated by insignificant energy barriers. 3. The voltage dependence of the off‐ (exit) rates is very similar in amplitude for all the four experimental configurations (e‐fold change per approximately 25 mV depolarization or hyperpolarization). This strong voltage dependence in every configuration cannot be explained by any Ca2+ energy profile alone and must include a certain contribution from Li+. The mechanism underlying such a contribution seems to reside in the enhancement effect of Li+ on the exist of Ca2+. 4. The on‐rates (blocking rates) for external Ca2+ are always fast no matter whether the Li+ currents are outward or inward. In certain cases the rates even approach the diffusion‐controlled limit (approximately 10(9) M‐1 S‐1). This suggests that the high‐affinity sites are very easily accessible from the outside, and probably there is no other ionic site located between the external pore mouth and the high‐affinity sites. 5. The on‐rates for internal Ca2+ are fast and voltage independent in outward Li+ currents, but are very slow and strongly voltage dependent in inward Li+ currents.(ABSTRACT TRUNCATED AT 400 WORDS)
Sound transmission across locally resonant honeycomb sandwich meta-structures with large spatial periodicity
Authors: Jin Yang , Wang Yu-Zhou , Li Xing-Yu , Lin Zhuang , Wu Qian-Qian , Wu Lin-Zhi
Published: October 2023

Honeycomb sandwich structures have been widely used in the field of engineering owing to their outstanding mechanical properties. However, for a honeycomb sandwich structure with large spatial periodicity, there is a low-frequency sound insulation valley. Here, the sound transmission across locally resonant honeycomb sandwich meta-structures was investigated to overcome this sound-insulation valley. An analytical model was developed based on the space-harmonic approach and the low-frequency sound insulation valley was determined analytically and numerically. The results indicate that the resonator distributed at the center of the face panel has a significant impact on the sound transmission performance of the honeycomb sandwich structure, whereas the resonator distributed on the wall of the honeycomb core does not contribute to overcoming this sound-insulation valley. Based on the research results, a design strategy for overcoming this sound-insulation valley was determined by tuning the damping parameter and constructing graded resonators. Moreover, sound transmission under the excitation of oblique incidence sound waves was also investigated. Compared with the method of filling porous materials, the proposed design method is more effective, and more importantly, the mass of the resonator is only 1.23% of that of the porous materials.
Multipitch estimation based on the iterative detection and separation of note events from single-channel polyphonic recordings
Authors: Delgado Castro Alejandro , Szymanski John E.
Published: October 2023

Multiple fundamental frequency estimation has been extensively used in applications such as melody extraction, music transcription, instrument identification, and source separation. This paper presents an approach based on the iterative detection and extraction of note events, which are considered to be harmonic sounds characterised by a continuous pitch trajectory. Note events are assumed to be associated with musical notes being played by a single instrument, and their pitch trajectories are iteratively estimated. In every iteration, the pitch contour of the predominant note event is selected from a set of pitch estimates and used to separate its spectral energy from the input mixture in order to obtain a residual signal, which is then used as input in the next iteration. This iterative process stops when the energy of the residual is below a significance threshold. The pitch trajectories of all detected note events are then revised and reassembled to form the final set of pitch estimates for the original audio input. Evaluation of performance is conducted in different scenarios to show the potential of the proposed system, both in terms of its accuracy, and also as an initial stage in other complex tasks, such as note tracking and multipitch streaming.
Mating sounds in the two-spotted goby, Pomatoschistus flavescens: Effects of water temperature on acoustic features
Authors: Millot Morgane , Faria Ana M. , Amorim M. Clara P.
Published: October 2023

Acoustic signals in teleost fishes play a fundamental role in reproduction. As fish are ectothermic animals, temperature has the potential to change their signal production and detection, with further implications for mating interactions. In this study, we describe the mating sounds made by the two-spotted goby, Pomatoschistus flavescens, for the first time and further investigate the effect of temperature on the acoustic features. Courtship sounds of 15 two-spotted goby males were recorded at three different temperatures: 16 °C, 19 °C, and 21 °C. As seen for other marine gobies, two-spotted goby produced two courtship sounds: drums and thumps. Drums showed similar acoustic features to other Pomatoschistus species already studied. Calling rates for both kinds of sound were not affected by the increases in temperature. However, pulse rate increased from 16 °C to 19 °C and stabilised between 19 °C and 21 °C, suggesting that two-spotted gobies reached their physiological limits at 19 °C. Spectral features were also affected by temperature, presenting higher values at 19 °C. Whether or not the observed changes in acoustic features with temperature lead to changes in mating remains to be addressed. Studies like the present one are fundamental to better comprehend how reproduction will be affected by global warming in soniferous fishes.
The intensities of vowels and plosive bursts and their impact on text intelligibility in singing
Authors: Vurma Allan , Meister Einar , Meister Lya , Ross Jaan , Raju Marju , Kala Veeda , Dede Tuuri
Published: October 2023

In classical singing, there are often problems with the intelligibility of sung text. The present study aims to test the hypotheses that (1) in loud operatic singing, compared with speaking, the intensity of voiceless plosives increases less than the intensity of vowels, leading to poorer recognition of plosives; and (2) pronouncing the plosive bursts with greater intensity improves their recognition. The acoustic analysis of nine opera arias in Italian from the Classical and Romantic periods performed by ten classically trained singers showed that the average difference in the intensity of vowels when sung and spoken was 14.6 dB [standard deviation (SD) = 7.2 dB], while the difference in the intensity of voiceless plosive bursts was only 6.6 dB (SD = 6 dB). In a perception test with 73 participants, increasing the intensity of the plosive bursts generally improved the recognition of plosives in the sung /a–plosive–a/ sequences, but mainly when reverberation and/or pink noise imitating instrumental accompaniments were added to the stimuli. At the same time, recognition of plosives was often better than chance even when the plosive burst was missing and replaced by silence.
Evaluating machine learning architectures for sound event detection for signals with variable signal-to-noise-ratios in the Beaufort Sea
Authors: Ibrahim Malek , Sagers Jason D. , Ballard Megan S. , Le Minh , Koutsomitopoulos Vasilis
Published: October 2023

This paper explores the challenging polyphonic sound event detection problem using machine learning architectures applied to data recorded in the Beaufort Sea during the Canada Basin Acoustic Propagation Experiment. Four candidate architectures were investigated and evaluated on nine classes of signals broadcast from moored sources that were recorded on a vertical line array of hydrophones over the course of the yearlong experiment. These signals represent a high degree of variability with respect to time-frequency characteristics, changes in signal-to-noise ratio (SNR) associated with varying signal levels as well as fluctuating ambient sound levels, and variable distributions, which resulted in class imbalances. Within this context, binary relevance, which decomposes the multi-label learning task into a number of independent binary learning tasks, was examined as an alternative to the conventional multi-label classification (MLC) approach. Binary relevance has several advantages, including flexible, lightweight model configurations that support faster model inference. In the experiments presented, binary relevance outperformed conventional MLC approach on classes with the most imbalance and lowest SNR. A deeper investigation of model performance as a function of SNR showed that binary relevance significantly improved recall within the low SNR range for all classes studied.
Human cerebrospinal fluid affects chemoradiotherapy sensitivities in tumor cells from patients with glioblastoma
Authors: Stringer Brett W. , De Silva Manam Inushi , Greenberg Zarina , Noreña Puerta Alejandra , Adams Robert , Milky Bridget , Zabolocki Michael , van den Hurk Mark , Ebert Lisa M. , Fairly Bishop Christine , Conn Simon J. , Kichenadasse Ganessan , Michael Michael Z. , Ormsby Rebecca J. , Poonoose Santosh , Bardy Cedric
Published: October 2023

Cancers in the central nervous system resist therapies effective in other cancers, possibly due to the unique biochemistry of the human brain microenvironment composed of cerebrospinal fluid (CSF). However, the impact of CSF on cancer cells and therapeutic efficacy is unknown. Here, we examined the effect of human CSF on glioblastoma (GBM) tumors from 25 patients. We found that CSF induces tumor cell plasticity and resistance to standard GBM treatments (temozolomide and irradiation). We identified nuclear protein 1 (NUPR1), a transcription factor hampering ferroptosis, as a mediator of therapeutic resistance in CSF. NUPR1 inhibition with a repurposed antipsychotic, trifluoperazine, enhanced the killing of GBM cells resistant to chemoradiation in CSF. The same chemo-effective doses of trifluoperazine were safe for human neurons and astrocytes derived from pluripotent stem cells. These findings reveal that chemoradiation efficacy decreases in human CSF and suggest that combining trifluoperazine with standard care may improve the survival of patients with GBM.
Enhanced causal effect of ecosystem photosynthesis on respiration during heatwaves
Authors: Ping Jiaye , Cui Erqian , Du Ying , Wei Ning , Zhou Jian , Wang Jing , Niu Shuli , Luo Yiqi , Xia Jianyang
Published: October 2023

Because of global warming, Earth’s ecosystems have been experiencing more frequent and severe heatwaves. Heatwaves are expected to tip terrestrial carbon sequestration by elevating ecosystem respiration and suppressing gross primary productivity (GPP). Here, using the convergent cross-mapping technique, this study detected positive bidirectional causal effects between GPP and respiration in two unprecedented European heatwaves. Heatwaves enhanced the causal effect strength of GPP on respiration rather than respiration on GPP across 40 site-years of observations. Further analyses and global simulations revealed spatial heterogeneity in the heatwave response of the causal link strength between GPP and respiration, which was jointly driven by the local climate and vegetation properties. However, the causal effect strength of GPP on respiration showed considerable uncertainties in CMIP6 models. This study reveals an enhanced causal link strength between GPP and respiration during heatwaves, shedding light on improving projections for terrestrial carbon sink dynamics under future climate extremes.
Intranasal parainfluenza virus type 5 (PIV5)–vectored RSV vaccine is safe and immunogenic in healthy adults in a phase 1 clinical study
Authors: Spearman Paul , Jin Hong , Knopp Kristeene , Xiao Peng , Gingerich Maria Cristina , Kidd Jamie , Singh Karnail , Tellier Marinka , Radziewicz Henry , Wu Samuel , McGregor Matthew , Freda Barbara , Wang Zhaoti , John Susan P. , Villinger Francois J. , He Biao
Published: October 2023

Respiratory syncytial virus (RSV) can lead to serious disease in infants, and no approved RSV vaccine is available for infants. This first in-human clinical trial evaluated a single dose of BLB201, a PIV5-vectored RSV vaccine administrated via intranasal route, for safety and immunogenicity in RSV-seropositive healthy adults (33 to 75 years old). No severe adverse events (SAEs) were reported. Solicited local and systemic AEs were reported by <50% of participants and were mostly mild in intensity. Vaccine virus shedding was detected in 17% of participants. Nasal RSV-specific immunoglobulin A responses were detected in 48%, the highest level observed in adults among all intranasal RSV vaccines evaluated in humans. RSV-neutralizing antibodies titers in serum rose ≥1.5-fold. Peripheral blood RSV F–specific CD4
+
and CD8
+
T cells increased from ≤0.06% at baseline to ≥0.26 and 0.4% after vaccination, respectively, in >93% participants. The safety and immunogenicity profile of BLB201 in RSV-seropositive adults supports the further clinical development of BLB201.
Assistive robotics should seamlessly integrate humans and robots
Authors: Weber Douglas , Matsiko Amos
Published: October 2023

Better integration of assistive robots with humans and adoption of a user-centric approach in their development will improve performance.
Prenatal Zika virus infection has sex-specific effects on infant physical development and mother-infant social interactions
Authors: Moadab Gilda , Pittet Florent , Bennett Jeffrey L. , Taylor Christopher L. , Fiske Olivia , Singapuri Anil , Coffey Lark L. , Van Rompay Koen K. A. , Bliss-Moreau Eliza
Published: October 2023

There is enormous variation in the extent to which fetal Zika virus (fZIKV) infection affects the developing brain. Despite the neural consequences of fZIKV infection observed in people and animal models, many open questions about the relationship between infection dynamics and fetal and infant development remain. To further understand how ZIKV affects the developing nervous system and the behavioral consequences of prenatal infection, we adopted a nonhuman primate model of fZIKV infection in which we inoculated pregnant rhesus macaques and their fetuses with ZIKV in the early second trimester of fetal development. We then tracked their health across gestation and characterized infant development across the first month of life. ZIKV-infected pregnant mothers had long periods of viremia and mild changes to their hematological profiles. ZIKV RNA concentrations, an indicator of infection magnitude, were higher in mothers whose fetuses were male, and the magnitude of ZIKV RNA in the mothers’ plasma or amniotic fluid predicted infant outcomes. The magnitude of ZIKV RNA was negatively associated with infant growth across the first month of life, affecting males’ growth more than females’ growth, although for most metrics, both males and females evidenced slower growth rates as compared with control animals whose mothers were not ZIKV inoculated. Compared with control infants, fZIKV infants also spent more time with their mothers during the first month of life, a social behavior difference that may have long-lasting consequences on psychosocial development during childhood.
Whole genome sequencing-based identification of human tuberculosis caused by animal-lineage
Mycobacterium orygis
Authors: Islam Md Rashedul , Sharma Meenu K. , KhunKhun Rupinder , Shandro Cary , Sekirov Inna , Tyrrell Gregory J. , Soualhine Hafid
Published: October 2023

A recently described member of the
Mycobacterium tuberculosis
complex (MTBC) is
Mycobacterium orygis
, which can cause disease primarily in animals but also in humans. Although
M. orygis
has been reported from different geographic regions around the world, due to a lack of proper identification techniques, the contribution of this emerging pathogen to the global burden of zoonotic tuberculosis is not fully understood. In the present work, we report single nucleotide polymorphism (SNP) analysis using whole genome sequencing (WGS) that can accurately identify
M. orygis
and differentiate it from other members of the MTBC species. WGS-based SNP analysis was performed for 61 isolates from different provinces in Canada that were identified as
M. orygis
. A total of 56
M
.
orygis
sequences from the public databases were also included in the analysis. Several unique SNPs in the
gyrB
,
PPE55
,
Rv2042c
,
leuS
,
mmpL6
, and
mmpS6
genes were used to determine their effectiveness as genetic markers for the identification of
M. orygis
. To the best of our knowledge, five of these SNPs, viz.,
gyrB
277
(A→G),
gyrB
1478
(T→C),
leuS
1064
(A→T),
mmpL6
486
(T→C), and
mmpS6
334
(C→G), are reported for the first time in this study. Our results also revealed several SNPs specific to other species within MTBC. The phylogenetic analysis shows that the studied genomes were genetically diverse and clustered with
M. orygis
sequences of human and animal origin reported from different geographic locations. Therefore, the present study provides a new insight into the high-confidence identification of
M. orygis
from MTBC species based on WGS data, which can be useful for reference and diagnostic laboratories.
Microbiological characterization of
Pneumocystis jirovecii
pneumonia using quantitative PCR from nasopharyngeal specimens: a retrospective study in a Canadian province from 2019 to 2023
Authors: Lieu Anthony , Lee Todd C. , Lawandi Alexander , Tellier Raymond , Cheng Matthew P. , Dufresne Philippe J.
Published: October 2023

Bronchoalveolar lavage is usually employed for molecular diagnosis of
Pneumocystis jirovecii
but requires a specialized procedure. By contrast, nasopharyngeal (NP) specimens are easily obtained. In this retrospective study of 35 patients with paired NP and bronchoscopy specimens, NP specimens had a 100% negative percent agreement (95% CI 80.5–100) but only 72.2% positive percent agreement (95% CI 46.5–90.3).
Transfer-bound community college students’ biology identity and perception of teaching
Authors: Teshera-Levye Jennifer , Atchison Tammy , Callis-Duehl Kristine , Gould Thomas , Lichti Deborah , Scemama Jean-Luc , Stiller John , Vance-Chalcraft Heather D.
Published: October 2023

Community colleges are frequently an affordable, accessible entrance to a Science, Technology, Engineering, and Mathematics (STEM) education and career, but the transition from a 2-year program to a 4-year institution can be tumultuous. In this mixed-methods study, we explore the experiences of transfer and prospective transfer students. Through surveys and interviews, we identify the challenges faced by and the supports desired by biology transfer students. We describe how community college students perceive their introductory biology courses, and we compare the biology identity and self-efficacy of these students to peers at a 4-year institution. Students expressed uncertainty about what to expect from the transfer experience, and they benefitted from interventions that made the university experience more concrete or clarified their expectations. We found that community college students are just as interested in biology as peers at a 4-year university, but they are significantly less likely to believe that others recognize them as “biology people” and report less self-efficacy regarding biology courses. Students felt particularly well-prepared for transfer after community college biology courses they described as “rigorous” and “demanding,” especially because students expressed that the community college environment helped support them through the challenges of higher education.
Functional characterization of
Microplitis demolitor
bracovirus genes that encode nucleocapsid components
Authors: Lorenzi Ange , Arvin Michael J. , Burke Gaelen R. , Strand Michael R.
Published: October 2023

Bracoviruses (BVs) are endogenized nudiviruses in parasitoid wasps of the microgastroid complex (order Hymenoptera: Family Braconidae). BVs produce replication-defective virions that adult female wasps use to transfer DNAs encoding virulence genes to parasitized hosts. Some BV genes are shared with nudiviruses and baculoviruses with studies of the latter providing insights on function, whereas other genes are only known from nudiviruses or other BVs which provide no functional insights. A proteomic analysis of
Microplitis demolitor
bracovirus (MdBV) virions recently identified 16 genes encoding nucleocapsid components. In this study, we further characterized most of these genes. Some nucleocapsid genes exhibited early or intermediate expression profiles, while others exhibited late expression profiles. RNA interference (RNAi) assays together with transmission electron microscopy indicated
vp39
,
HzNVorf9-like2
,
HzNVorf93-like
,
HzNVorf106-like
,
HzNVorf118-like
,
and 27b
are required to produce capsids with a normal barrel-shaped morphology. RNAi knockdown of
vlf-1a
,
vlf-1b-1
,
vlf-1b-2
,
int-1,
and
p6.9-1
did not alter the formation of barrel-shaped capsids but each reduced processing of amplified proviral segments and DNA packaging as evidenced by the formation of electron translucent capsids. All of the genes required for normal capsid assembly were also required for proviral segment processing and DNA packaging. Collectively, our results deorphanize several BV genes with previously unknown roles in virion morphogenesis.

IMPORTANCE

Understanding how bracoviruses (BVs) function in wasps is of broad interest in the study of virus evolution. This study characterizes most of the
Microplitis demolitor
bracovirus (MdBV) genes whose products are nucleocapsid components. Results indicate several genes unknown outside of nudiviruses and BVs are essential for normal capsid assembly. Results also indicate most MdBV tyrosine recombinase family members and the DNA binding protein
p6.9-1
are required for DNA processing and packaging into nucleocapsids.
HPV38 impairs UV-induced transcriptional activation of the IL-18 pro-inflammatory cytokine
Authors: Ceraolo Maria Grazia , Romero-Medina Maria Carmen , Gobbato Simone , Melita Giusi , Krynska Hanna , Sirand Cecilia , Gupta Purnima , Viarisio Daniele , Robitaille Alexis , Marvel Jacqueline , Tommasino Massimo , Venuti Assunta , Gheit Tarik
Published: October 2023

Increasing evidence suggests that the beta genus of human papillomavirus (β-HPV) cooperates with ultraviolet B (UVB) radiation in inducing non-melanoma skin cancer (NMSC). For instance, expression of E6 and E7 oncoproteins from cutaneous human papillomavirus type 38 (HPV38) in a transgenic mouse model (Tg38) leads to the development of squamous cell carcinoma (SCC) after chronic UVB exposure. Transcriptomic analysis of the Tg38 SCC samples revealed a deregulation of inflammasome pathway-related genes such as IL-18, which is consistent with the well-known capability of several oncogenic viruses to modulate the immune response, in order to efficiently produce new progeny. However, the mechanism at the gene expression level by which UVB and HPV38 synergize and modulate the innate immune response has not been elucidated yet. Here, we propose a new molecular mechanism for the regulation of the IL-18 promoter that involves direct binding of p53 to specific response elements. This mechanism seems to be impaired in the presence of the β-HPV38 oncoproteins. Instead, a newly described inhibitory complex formed by DNA methyltransferase 1 (DNMT1)/PKR/ΔNp73α is recruited to the region formerly occupied by p53 in primary keratinocytes. Together, these results corroborate our hypothesis that β-HPV38 plays an important role in the inhibition of the ultraviolet-induced inflammasome response. This downregulation is likely to impair the ability of keratinocytes to recruit the immune cell population at the UVB-exposed area, causing a defect in the clearance of cells harboring DNA damage and promoting a favorable environment for the progression of NMSC.

IMPORTANCE

Here, we demonstrate that the direct binding of p53 on the IL-18 promoter region regulates its gene expression. However, the presence of E6 and E7 from human papillomavirus type 38 impairs this mechanism via a new inhibitory complex formed by DNA methyltransferase 1 (DNMT1)/PKR/ΔNp73α, which binds to the region formerly occupied by p53 in primary keratinocytes.
Parenting stress and health-related quality of life among parents of extremely preterm born early adolescents in England: a cross-sectional study
Authors: Suonpera Emmi , Lanceley Anne , Ni Yanyan , Marlow Neil
Published: October 2023

Objective

To determine whether extremely preterm (EP) birth exerts persisting effects on parents in early adolescence.

Design

Cross-sectional survey conducted between March 2017 and October 2018.

Setting

Evaluation of a longitudinal population-based birth cohort in England at 11 years of age (EPICure2@11 Study).

Participants

Parents of EP (<27 weeks of gestation) adolescents and control parents of term born (≥37 weeks of gestation) classmates of similar age and sex.

Main outcome measures

The Parenting Stress Index Short Form (PSI-4-SF) and the Short Form Health Survey (SF-12v1).

Results

The 163 EP and 125 comparison respondents were most commonly mothers in their mid-40s. EP parents reported higher total parenting stress scores compared with controls, overall (adjusted difference in means: 14 (95% CI 9 to 20)) and after exclusion of moderate and severe child disability and multiples (9 (95% CI 3 to 15). Average physical and mental health-related quality of life scores were similar in the two groups (adjusted difference in means physical health: −2 (95% CI −4 to 1) and mental health: −1 (95% CI −4 to 1)). Among EP parents, 12% (20/164) reported the combination of high parenting stress and low mental health scores. With increasing child age, parenting stress scores for preterm parents were lower in contrast to controls who reported increasing parenting stress.

Conclusions

In early adolescence, compared with parents of term-born children, EP parents experience increased levels of parenting stress that are particularly high among a proportion of parents and associated with lower mental health-related quality of life. Practitioner awareness of this continuing risk throughout childhood is important to support parental abilities and well-being.
Diagnostic value of rapid test for malaria among febrile neonates in a tertiary hospital in North-East Nigeria: a prospective cross-sectional study
Authors: Adeniji Yasangra Rabo , Jalo Iliya , Okonkwo Ikechukwu , Poksireni Mercy Raymond , Manga Mohammed , Wariri Oghenebrume , Alhassan Halima Abdulkarim , Warnow Elon Isaac
Published: October 2023

Objective

The WHO recommends testing using microscopy or rapid diagnostic test (RDT) before treatment for malaria. However, the use of RDT to diagnose neonatal malaria has not been widely validated with most studies limited to the first week of life. Thus, we conducted this study to determine the utility of RDT in the diagnosis of congenital and acquired malaria in febrile neonates in Nigeria.

Design

This prospective cross-sectional descriptive study consecutively recruited 131 febrile neonates at the Special Care Baby Unit (SCBU) of the Federal Teaching Hospital Gombe, Nigeria. All study participants concurrently had RDT (HRP2, LDH) and malaria microscopy. The performance of both methods was then compared.

Result

Seventy-eight of 131 neonates tested for malaria by blood smear microscopy demonstrated malaria parasites; a prevalence of 59.5%. Parasite count ranged from 16 to 520 /μL and the median parasite count was 81.0 /μL with IQR (40.0–134.5). The majority of patients (93.5%) had low-density parasitaemia (≤2+). All species identified werePlasmodium falciparum. None of the 131 neonates tested positive on RDT. The sensitivity and positive predictive value of RDT for neonatal malaria was zero. Congenital malaria was the most common form of neonatal malaria, accounting for 75.6%, while acquired and transfusion-related malaria were estimated at 12.8% and 11.6%, respectively.

Conclusion

The RDT used in this study was not sensitive in the diagnosis of congenital or acquired neonatal malaria; therefore, microscopy remains the preferred method of diagnosis of neonatal malaria.
Delayed myelopathy in a child following organic phosphate poisoning
Authors: Al Amrani Fatma , Wali Yasser , Mittal Alok , Al Futaisi Amna
Published: October 2023

We report a rare manifestation of delayed organophosphate (OP) poisoning in a male patient in his early childhood. After initially presenting with a cholinergic crisis after OP exposure, the patient returned 3 weeks later with paraparesis and difficulty with bladder control. The results of the MRI of the spine and brain as well as the nerve conduction studies were normal. Myelopathy induced by OP poisoning should be considered in any patient with a history of OP exposure and a presentation of paraparesis. At most recent follow-up, the patient had full bladder control and could walk without assistance. However, he demonstrated circumduction while walking with upper motor neuron signs. Furthermore, he had mild Achilles tendon contractures on both sides. To enable early detection, neurologists and paediatricians should be aware of this uncommon complication of OP poisoning which may influence neurological outcome.
Device-measured physical activity, sedentary time, and risk of all-cause mortality: an individual participant data analysis of four prospective cohort studies
Authors: Sagelv Edvard H , Hopstock Laila Arnesdatter , Morseth Bente , Hansen Bjørge H , Steene-Johannessen Jostein , Johansson Jonas , Nordström Anna , Saint-Maurice Pedro F , Løvsletten Ola , Wilsgaard Tom , Ekelund Ulf , Tarp Jakob
Published: October 2023

Objectives

To examine whether moderate-to-vigorous physical activity (MVPA) modifies the association between sedentary time and mortality and vice versa, and estimate the joint associations of MVPA and sedentary time on mortality risk.

Methods

This study involved individual participant data analysis of four prospective cohort studies (Norway, Sweden, USA, baseline: 2003–2016, 11 989 participants ≥50 years, 50.5% women) with hip-accelerometry-measured physical activity and sedentary time. Associations were examined using restricted cubic splines and fractional polynomials in Cox regressions adjusted for sex, education, body mass index, smoking, alcohol, study cohort, cardiovascular disease, cancer, and/or diabetes, accelerometry wear time and age.

Results

6.7% (n=805) died during follow-up (median 5.2 years, IQR 4.2 years). More than 12 daily sedentary hours (reference 8 hours) was associated with mortality risk only among those accumulating <22 min of MVPA per day (HR 1.38, 95% CI 1.10 to 1.74). Higher MVPA levels were associated with lower mortality risk irrespective of sedentary time, for example, HR for 10 versus 0 daily min of MVPA was 0.85 (95% CI 0.74 to 0.96) in those accumulating <10.5 daily sedentary hours and 0.65 (95% CI 0.53 to 0.79) in those accumulating ≥10.5 daily sedentary hours. Joint association analyses confirmed that higher MVPA was superior to lower sedentary time in lowering mortality risk, for example, 10 versus 0 daily min of MVPA was associated with 28–55% lower mortality risk across the sedentary time spectrum (lowest risk, 10 daily sedentary hours: HR 0.45, 95% CI 0.31 to 0.65).

Conclusions

Sedentary time was associated with higher mortality risk but only in individuals accumulating less than 22 min of MVPA per day. Higher MVPA levels were associated with lower mortality risk irrespective of the amount of sedentary time.
Filling the evidence void: exploration of coach and healthcare provider experiences working with pregnant and postpartum elite athletes – a qualitative study
Authors: Davenport Margie H , Ray Lauren , Nesdoly Autumn , Thornton Jane S , Khurana Rshmi , McHugh Tara-Leigh F
Published: October 2023

Objective

Recent research grounded in the experiences of elite female athletes has shed light on the complex challenges of navigating sport environments that do not support or value pregnant or postpartum athletes. The purpose of this study was to explore the unique experiences of coaches and healthcare providers working with pregnant and postpartum elite athletes, and to identify actionable steps for research, policy and culture change to support them.

Methods

Sixteen participants (five coaches, three physicians and eight physiotherapists), who have worked with pregnant and/or postpartum elite athletes within the last 5 years, participated in this qualitative study. Thirteen participants self-identified as women, and three as men. Data were generated via semistructured one-on-one interviews that were audiorecorded, transcribed verbatim and analysed through a process of content analysis.

Results

The findings of this research are represented by five main themes: (a) lack of female athlete reproductive research, (b) need for evidence-informed education and training, (c) need to develop evidence-based progression for sport participation in pregnancy and postpartum, (d) open communication to support athlete-centred care and (e) essential supports and changes required for pregnant/postpartum athletes.

Conclusion

Findings from this study, which are grounded in the unique perspectives of coaches and healthcare providers, outline specific recommendations to inform policy and practices that support athletes through the perinatal period, such as developing evidence-based return-to-sport protocols.