bluuebunny/crossref_metadata_2025 huggingface dataset:
MdILL6 regulates xylem and vessel development to control internode elongation in spur‐type apple
Authors: Gao Xiuhua , Sun Hongwei , Liu Yandong , Zhang Shubiao , Liu Yu , Tahir Muhammad Mobeen , Tong Lu , Zhang Pan , Toktonazarovich Turgunbayev Kubanychbek , Lv Yanrong , Ma Juanjuan , Zhang Dong , Mao Jiangping
Published: November 2024

Spur‐type varieties play an important role in facilitating high‐density plantings. However, the underlying mechanisms of internode elongation in spur‐type varieties are poorly understood. In this research, we investigated the morphological phenotype of annual shoots in four spur‐type varieties (‘Miyazak’, ‘Jinfu 18’, ‘Yanfu No. 6’, and ‘Liquan spur’) and four standard‐type varieties (‘Aomorifu’, ‘Shou Fuji’, ‘Yanfu No. 10’, and ‘Yanfu No. 3’). Compared with standard‐type varieties, spur‐type varieties had a shorter shoot length, an average internode length and a smaller xylem size. The content of Jasmonic acid (JA) and Jasmonic acid isoleucine (JA‐Ile) significantly increased in spur‐type varieties, accompanied by an increase in the expression of JA biosynthesis and signal transduction genes. Exogenous methyl jasmonate (MeJA) inhibited plant height, xylem size, and vessel area. Additionally, we identified an IAA‐Leucine Resistant1‐like Hydrolase family member, MdILL6, which was highly expressed in spur‐type varieties and mature stems. MdILL6 was mainly expressed in the shoot tips and stem, and its protein was located on the endoplasmic reticulum. Overexpression of MdILL6 in apple inhibited plant height and average internode length by decreasing xylem size and vessel area. Our results revealed a molecular mechanism of spur‐type variety development affected by the JA pathway and suggest strategies for genetic improvement and regulation of spur‐type varieties.
ANTICONVULSANT EFFECT OF ISOLATED COMPOUNDS FROM THE LEAVES OF GLOBIMETULA BRAUNII ENGLER VAN TIEGH (LORANTHACEAE) IN MICE AND CHICKS
Authors: Ja’afar Muhammad Kamal , Jamil Shajarahtunnur , Basar Norazah , Magaji Mohammed Garba
Published: November 2024

The anticonvulsant evaluation of globrauneine A (1), globrauneine C (2) globrauneine D (3), globrauneine F (4), lupeol (5), β-sitosterol (6), (1R,5S,7S)-7-[2-(4-hydroxyphenyl) ethyl]-2,6-dioxabi-cyclo [3. 3.1]-nonan-3-one (7), dodoneine (8), quercetin (9) and rutin (10) from Globimetula braunii leaves were analyzed with the aid of pentylenetetrazole-induced seizure test in mice (PTZ) and maximal electroshock seizure test in chicks (MEST), while the neurotoxicity was evaluated using the beam walking assay in mice. 50% of the tested mice were protected by Globrauneine A (1) and dodoneine (8) against PTZ-induced mortality. The mean onset of clonic spasm of the unprotected animals was increased by Quercetin (9) and also the mice were differentially protected against mortality. The tested compounds also produced significant (p<0.05) increase in the mean onset of seizure against pentylenetetrazole-induced seizure. The chicks were not protected by the tested compounds against MEST and the recovery time was not significantly reduced. In the beam assay, with the exception of dodoneine (8), the number of foot slips and the time taken to complete the task was not significantly changed by the tested isolated compounds, suggesting that the observed activities are not due to general CNS depression. The results suggest mild protective effects of these isolated compounds against seizure which might be useful in the control of petit mal epilepsy.
CRUMPLE ZONE MODELLING OF PASSENGER VEHICLE USING MULTIPLE KELVIN MODEL AND OPTIMIZED WITH PARTICLE SWARM OPTIMIZATION
Authors: Hudha Khisbullah , Abd Kadir Zulkiffli , Mohd Alawi Alawiyah Hasanah , Amer Noor Hafizah , Ku Ahmad Ku Zarina
Published: November 2024

This paper presents the mathematical modelling of a vehicle crash system using a mass-spring-damper approach to simulate the behavior of a real vehicle during a frontal impact. A Multiple Kelvin model is developed to represent a real vehicle crash situation where the impact is introduced on the frontal vehicle body. The modelling process of Multiple Kelvin model is based on a single Kelvin model that developed into a set of seven mass-spring-damper systems representing the front crumple zone of a real vehicle. The model is then optimized for the parameters k and c using an optimization method namely Particle Swarm Optimization (PSO) algorithm in MATLAB-Simulink. The simulation results demonstrate deformation and acceleration responses closely follow the previous experimental results where the parameters namely Ni, Np, and iw are varied to enhance the model's precision through the calculation of error of 12.15 using parameters Ni = 80, Np = 40 and iw = 0.9.
ACTINOBACTERIAL DIVERSITY DETERMINATION IN MALAYSIAN BRIS (BEACH RIDGES INTERSPERSED WITH SWALES) SOIL BY CULTURE-DEPENDENT APPROACH
Authors: Hairi Hamizah Hazmeen , Ahmad Amirah , Azman Muhammad Adib Zakwan , Idris Hamidah , Abdullah Muhd Danish-Daniel , Hassan Mohd Yazid , Mohamad Zin Noraziah
Published: November 2024

Globally, the rapid emergence of antibiotic-resistant bacteria poses a major threat to public health, threatening the effectiveness of antibiotics. Addressing the crisis of antimicrobial resistance requires urgency in new drug discovery and the effort in finding novel compounds is dramatically evolving. However, one of the main obstacles is the rediscovery of known compounds from natural resources. To overcome this challenge, exploring underexploited location for new resource of actinomycetes, such as Beach Ridges Interspersed with Swales (BRIS) soil in Malaysia, was selected. Soil samples from Jambu Series and Rudua Series in Setiu, Terengganu were collected and analysed. A total of 87 actinomycetes strains were isolated on yeast malt agar (ISP2), Actinomyces agar and Zobell marine agar, with the highest number from the Jambu series using serial dilution and spread plate method. Antimicrobial screening revealed that 31 isolates exhibited activity against ESKAPE pathogens, with 28 and 12 isolates showing activity against Gram-positive and Gram-negative bacteria, respectively. These isolates showed strong inhibiting response towards one or more ESKAPE pathogens. This study highlights the potential of BRIS soil as an underexploited habitat for discovering actinobacterial communities which could lead to the discovery of a new potential antimicrobial producer to serve as novel drug leads.
THE EXTERNAL DRAFT TUBE GASLIFT BIOREACTOR: HYDRODYNAMIC CHARACTERISTICS AND PARAMETRIC OPTIMIZATION
Authors: Al-Mashhadani Mahmood K. H. , Al-Yaqoobi Atheer M. , Salman Rasha H.
Published: November 2024

Gaslift reactors are employed in several bioapplications due to their characteristics of cost-effectiveness and high efficiency. However, the nutrient and thermal gradient is one of the obstacles that stand in the way of its widespread use in biological applications. The diagnosis, analysis, and tracking of fluid paths in external draft tube gaslift bioreactor-type are the main topics of the current study. Several parameters were considered to assess the mixing efficiency such as downcomer-to-rizer diameter ratio (Ded/Dr), the position of the diffuser to the height of bioreactor ratio (Pd/Lr), and gas bubble size (Db). The multiple regression of liquid velocity indicates the optimal setting: Ded/Dr is (0.5), Pd/Lr is (0.02), and Db is (400) um.  However, for technical and operational reasons, it was necessary to make some changes in the optimal values obtained from the numerical equations. The study also revealed that the size of gas bubbles is the characteristic that has the greatest influence on the dynamic efficiency of the fluid inside the bioreactor, since, reducing the bubble size by half can enhance the improvement rate in the circulation of the liquid up to 35%.
Impaired oxytocin signalling in the central amygdala in rats with chronic heart failure
Authors: Althammer Ferdinand , Roy Ranjan K. , Kirchner Matthew K. , Lira Elba Campos , Schimmer Stephanie , Charlet Alexandre , Grinevich Valery , Stern Javier E.
Published: November 2024

Heart failure (HF) patients suffer from cognitive decline and mood impairments, but the molecular signals and brain circuits underlying these effects remain elusive. The hypothalamic neuropeptide oxytocin (OT) is critically involved in regulating mood, and OTergic signalling in the central amygdala (CeA) is a key mechanism that controls emotional responses including anxiety‐like behaviours. Still, whether an altered OTergic signalling contributes to mood disorders in HF remains unknown. To address this, we used an ischaemic rat HF model, along with a highly multidisciplinary approach, to mechanistically study multiple levels of the hypothalamus‐to‐CeA OTergic circuit in male rats with HF. We aimed to test the hypothesis that sustained activation of the OT system following an infarct leads to depletion of OT content in this pathway, with subsequent changes in OT receptor expression and blunted modulation of local GABAergic circuits. We found that most of OTergic innervation of the CeA originated from the supraoptic nucleus (SON). While no differences in the numbers of SON→CeA OTergic neurons was observed between sham and HF rats, we observed a blunted content and release of OT from axonal terminals within the CeA. Moreover, we report downregulation of neuronal and astrocytic OT receptors, and impaired OTR‐driven GABAergic synaptic activity within the CeA microcircuit of HF rats. We provide the first evidence that male HF rats display perturbations in the hypothalamus‐to‐amygdala OTergic circuit, laying the foundation for future translational studies targeting either the OT system or GABAergic amygdalar microcircuit to ameliorate mood impairments in rats or patients with chronic HF.

image

Key points

Heart failure patients suffer from cognitive decline, depression and mood impairments, but the underlying mechanisms remain elusive.

Acting within the central amygdala, the neuropeptide oxytocin regulates emotional responses, including anxiety‐like behaviours. However, whether changes in oxytocin signalling occurs during heart failure is unknown.

In this study, we used an ischaemic rat heart failure model to mechanistically study multiple levels of the hypothalamus‐to‐amygdala oxytocinergic circuit in this disease.

We report an overall blunted oxytocinergic signalling pathway in rats with heart failure, including blunted content and release of oxytocin from axonal terminals, downregulation of neuronal and astrocytic oxytocin receptors, and impaired oxytocin‐driven GABAergic synaptic activity within the central amygdala microcircuit of HF rats.

These studies shed light on mechanisms that contribute to mood disorders in cardiovascular disease states and help to identify potential molecular targets for their improved treatment.
OBTAINING ASEPTIC CULTURE IN VITRO OF RHODIOLA SEMENOWII L. FROM VARIOUS TYPES OF EXPLANTS
Authors: Raizer O. , Tagimanova D. , Baltabaeva K. , Khapilina O.
Published: November 2024

In vitro cultivation of callus cells allows for the stable production of secondary metabolites, being an alternative to the use of medicinal plant biomass from natural populations. Standardization of cultivation protocols and technological processes for the synthesis of secondary metabolites in vitro conditions determines significant interest in the use of tissue culture methods (PTC – Plant Tissue Culture). The aim of the study was to obtain an aseptic culture of Rhodiola semenowii in vitro from various types of explants, as well as the effect of the hormonal composition of the nutrient medium on the induction of callusogenesis in the culture of isolated organs of R. semenowii. As a result of the research, the optimal mode of obtaining R. semenovii aseptic cultures from various explants was determined. It has been shown that the use of 70% EtOH in combination with 0.01% HgCl2 or 20% NaClO makes it possible to obtain aseptic cultures from any type of R. semenovii explants. It has been established that the type of explant is R. semenovii influenced both the frequency of callus formation and the beginning of its formation. The least optimal types of R. semenovii explants are stem and rhizome segments, the frequency of callusogenesis varied from 5.8% to 75.6%. The induction of callusogenesis also depended on the hormonal composition of the nutrient medium: the highest percentage of callus formation in all types of explants was on media containing 0.5mg L−1 thidiazuron (TDZ) + 1.0 mg L−1 1-naphthaleneacetic acid (NAA) and 0.5mg L−12,4D + 2.0 mg L−1 6-Benzylaminopurine (BAP).
Vowel signatures in emotional interjections and nonlinguistic vocalizations expressing pain, disgust, and joy across languages
Authors: Ponsonnet Maïa , Coupé Christophe , Pellegrino François , Garcia Arasco Aitana , Pisanski Katarzyna
Published: November 2024

In this comparative cross-linguistic study we test whether expressive interjections (words like ouch or yay) share similar vowel signatures across the world's languages, and whether these can be traced back to nonlinguistic vocalizations (like screams and cries) expressing the same emotions of pain, disgust, and joy. We analyze vowels in interjections from dictionaries of 131 languages (over 600 tokens) and compare these with nearly 500 vowels based on formant frequency measures from voice recordings of volitional nonlinguistic vocalizations. We show that across the globe, pain interjections feature a-like vowels and wide falling diphthongs (“ai” as in Ayyy! “aw” as in Ouch!), whereas disgust and joy interjections do not show robust vowel regularities that extend geographically. In nonlinguistic vocalizations, all emotions yield distinct vowel signatures: pain prompts open vowels such as [a], disgust schwa-like central vowels, and joy front vowels such as [i]. Our results show that pain is the only affective experience tested with a clear, robust vowel signature that is preserved between nonlinguistic vocalizations and interjections across languages. These results offer empirical evidence for iconicity in some expressive interjections. We consider potential mechanisms and origins, from evolutionary pressures and sound symbolism to colexification, proposing testable hypotheses for future research.
Speech recognition in adverse conditions by humans and machines
Authors: Patman Chloe , Chodroff Eleanor
Published: November 2024

In the development of automatic speech recognition systems, achieving human-like performance has been a long-held goal. Recent releases of large spoken language models have claimed to achieve such performance, although direct comparison to humans has been severely limited. The present study tested L1 British English listeners against two automatic speech recognition systems (wav2vec 2.0 and Whisper, base and large sizes) in adverse listening conditions: speech-shaped noise and pub noise, at different signal-to-noise ratios, and recordings produced with or without face masks. Humans maintained the advantage against all systems, except for Whisper large, which outperformed humans in every condition but pub noise.
Impact of Fecal Organic Acid Profile Before Training on Athletic Performance Improvement After High-Intensity Interval Training
Authors: Yoshikawa Tomomi , Yokoyama Yukihiro , Sakai Akiyoshi , Kuno Takahiro , Nimura Yuji , Matsunami Hidetoshi
Published: November 2024

Purpose: This study sought to investigate the efficacy of Tabata-style high-intensity interval training (T-HIIT) on athletic performance in judoka and to determine the impact of the fecal organic acid profile before training on the improvement of athletic performance. Methods: Twenty males from Aichi University Judo Club (10 high-level competitors and 10 others) were included. Physical fitness tests such as the Uchikomi shuttle run, countermovement jump, squat jump, and chin-ups using a judo uniform were performed before and after T-HIIT. Fecal samples were collected before T-HIIT to measure the fecal concentration of organic acids. The fecal characteristics were categorized using the Bristol Stool Scale. Results: The mean number of repetitions of the Uchikomi shuttle run test significantly increased for all judoka following T-HIIT. However, improvements in other physical fitness tests varied, with some judoka showing improvements while others did not. The changes in countermovement jump (r = −.48, P = .029) and chin-ups using a judo uniform (r = −.45, P = .045) after T-HIIT were significantly negatively correlated with the fecal concentrations of succinic acid before T-HIIT. There was a significant correlation between the Bristol Stool Scale score and fecal concentrations of succinic acid (r = .45, P = .044). Compared with other compounds, the fecal concentrations of acetic acid and propionic acid were significantly greater in high-level competitors, while succinic acid concentrations tended to be lower. Conclusions: T-HIIT effectively improved the specialized endurance of the judoka. Modifying the fecal organic acid profile, especially the fecal succinic acid concentration, may enhance the efficacy of athletic performance improvements achieved by T-HITT.
Exploration of the Longitudinal Development of Physical Education Teacher Efficacy: Understanding the Key Influences Impacting Preservice Teachers
Authors: Magill Ceri , Cronin Colum , Polman Remco , Rudd James
Published: November 2024

Purpose: The purpose of this study is to investigate the longitudinal development of physical education (PE) teacher efficacy (TE) of preservice teachers. Method: Participants included 287 preservice teachers from six U.K. higher education institutions. Data were collected over 3 years using an online questionnaire that included a validated PE teaching efficacy scale with the same preservice teachers. Primary analysis included a one-way analysis of variance to examine variances across institutions, gender, and time, followed by four multilevel linear regression models using MLwiN. Results: No significant mean score differences were found in PE TE between entry point and program completion, F(5, 282) = 1.29, p = .268; F(5, 283) = 0.66, p = .65. Yet, significant differences in PE TE concerning gender, teaching, coaching, and voluntary experiences were found at the intralevel (p < .01). Discussion: The professionalization phase did not lead to significant advancements in PE TE. Findings support the necessity of a PE efficacy development model during professionalization.
Identification and characterization of the
Bacillus subtilis
spore germination protein GerY
Authors: Ramírez-Guadiana Fernando H. , Brogan Anna P. , Rudner David Z.
Published: November 2024

In response to starvation, endospore-forming bacteria differentiate into stress-resistant spores that can remain dormant for years yet rapidly germinate and resume growth when nutrients become available. To identify uncharacterized factors involved in the exit from dormancy, we performed a transposon-sequencing screen taking advantage of the loss of spore heat resistance that accompanies germination. We reasoned that transposon insertions that impair but do not block germination will lose resistance more slowly than wild type after exposure to nutrients and will therefore survive heat treatment. Using this approach, we identified most of the known germination genes and several new ones. We report an initial characterization of 15 of these genes and a more detailed analysis of one (
ymaF
). Spores lacking
ymaF
(renamed
gerY
) are impaired in germination in response to both L-alanine and L-asparagine, D-glucose, D-fructose, and K
+
. GerY is a soluble protein synthesized under
σ

E

control in the mother cell. A YFP-GerY fusion localizes around the developing and mature spore in a manner that depends on CotE and SafA, indicating that it is a component of the spore coat. Coat proteins encoded by the
gerP
operon and
gerT
are also required for efficient germination, and we show that spores lacking two or all three of these loci have more severe defects in the exit from dormancy. Our data are consistent with a model in which GerY, GerT, and the GerP proteins are required for efficient transit of nutrients through the coat to access the germination receptors, but each acts independently in this process.

IMPORTANCE

Pathogens in the orders Bacillales and Clostridiales resist sterilization by differentiating into stress-resistant spores. Spores are metabolically inactive and can remain dormant for decades, yet upon exposure to nutrients, they rapidly resume growth, causing food spoilage, food-borne illness, or life-threatening disease. The exit from dormancy, called germination, is a key target in combating these important pathogens. Here, we report a high-throughput genetic screen using transposon sequencing to identify novel germination factors that ensure the efficient exit from dormancy. We identify several new factors and characterize one in greater detail. This factor, renamed GerY, is part of the proteinaceous coat that encapsulates the dormant spore. Our data suggest that GerY enables efficient transit of nutrients through the coat to trigger germination.
SRCAP is involved in porcine reproductive and respiratory syndrome virus activated Notch signaling pathway
Authors: Ding Guofei , Li Yingchao , Li Dexin , Dou Mingyu , Fu Chaolun , Chen Ting , Cui Xinyu , Zhang Qin , Yang Pingping , Hou Yanmeng , Liu Sidang , Xiao Yihong
Published: November 2024

Porcine reproductive and respiratory syndrome viru
s
(PRRSV) is the cause of porcine reproductive and respiratory syndrome (PRRS); a disease of pigs, which results in great economic losses in the pork industry. The non-structural protein 4 (Nsp4), a 3C-like serine protease responsible for most non-structural protein processing, plays an essential role in PRRSV infection. We used label-free quantitative proteomics to elucidate the Nsp4 interactome and SRCAP was identified as one of the interactors. SRCAP facilitated PRRSV infection by activating non-canonical Notch signaling. The ATPase I–IV domain in SRCAP and the
122
VITEA
126
in Nsp4 were identified as the interacting sites. The infection of recovered mutant rTA-12/5A (
122
AAAAA
126
) could not activate Notch signaling. The results indicated that
122
VITEA
126
in Nsp4 were key sites to determine the function of SRCAP and their interaction. A function of Nsp4 in activating the Notch signaling pathway was discovered. Block Notch signaling pathway could inhibit PRRSV infection both
in vitro
and
in vivo
which may lead to the development of novel therapeutic antiviral strategies.

IMPORTANCE

In the present study, the interactome of the NSP4 originating from PRRSV was studied and SRCAP was confirmed as one of the interactors. Mechanism study showed the interaction of Nsp4 and SRCAP was found to facilitate PRRSV infection by activating non-canonical Notch signaling. ATPase Ⅰ–Ⅳ domain in SRCAP and the
122
VITEA
126
in Nsp4 were identified as the interacting sites that demined the activating of Notch signaling. Block Notch signaling pathway could inhibit PRRSV infection
in vitro
and
in vivo
which may be a new target for antiviral drug development.
Quantifying the impact of vaccination on transmission and diversity of influenza A variants in pigs
Authors: Li Chong , Culhane Marie R. , Schroeder Declan C. , Cheeran Maxim C-J. , Galina Pantoja Lucina , Jansen Micah L. , Torremorell Montserrat
Published: November 2024

Global evolutionary dynamics of influenza A virus (IAV) are fundamentally driven by the extent of virus diversity generated, transmitted, and shaped in individual hosts. How vaccination affects the degree of IAV genetic diversity that can be transmitted and expanded in pigs is unknown. To evaluate the effect of vaccination on the transmission of genetically distinct IAV variants and their diversity after transmission in pigs, we examined the whole genome of IAV recovered from the nasal cavities of pigs vaccinated with different influenza immunization regimens after being infected simultaneously by H1N1 and H3N2 IAVs using a seeder pig model. We found that the seeder pigs harbored more diversified virus populations than the contact pigs. Among contact pigs, H3N2 and H1N1 viruses recovered from pigs vaccinated with a single dose of an unmatched modified live vaccine generally accumulated more extensive genetic mutations than non-vaccinated pigs. Furthermore, the non-sterilizing immunity elicited by the single-dose-modified live vaccine may have exerted positive selection on H1 antigenic regions as we detected significantly higher nonsynonymous but lower synonymous evolutionary rates in H1 antigenic regions than non-antigenic regions. In addition, we observed that the vaccinated pigs shared significantly less proportion of H3N2 variants with seeder pigs than unvaccinated pigs. These results indicated that vaccination might reduce the impact of transmitted influenza variants on the overall diversity of IAV populations harbored in recipient pigs and that within-host genetic selection of IAV is more likely to occur in pigs vaccinated with improperly matched vaccines.

IMPORTANCE

Understanding how vaccination shapes the diversity of influenza variants that transmit and propagate among pigs is essential for designing effective IAV surveillance and control programs. Current knowledge about the transmission of IAV variants has primarily been explored in humans during natural infection. However, how immunity elicited by improperly matched vaccines affects the degree of IAV genetic diversity that can be transmitted and expanded in pigs at the whole-genome level is unknown. We analyzed IAV sequences from samples collected daily from experimentally infected pigs vaccinated with various protocols in a field-represented IAV co-infection model. We found that vaccine-induced non-sterilizing immunity might promote genetic variation on the IAV genome and drive positive selection at antigenic sites during infection. In addition, a smaller proportion of H3N2 viral variants were shared between seeder pigs and vaccinated pigs, suggesting the influence of vaccination on shaping the virus genomic diversity in recipient pigs during the transmission events.
Contrasting patterns of
Asaia
association with
Plasmodium falciparum
between field-collected
Anopheles gambiae
and
Anopheles coluzzii
from Cameroon
Authors: Tatsinkou Maffo Claudine Grâce , Sandeu Maurice Marcel , Tchoupo Micareme , Dondji Kamga Fleuriane Metissa , Mugenzi Leon M. J. , Njiokou Flobert , Hughes Grant L. , Wondji Charles S.
Published: November 2024

The widespread prevalence of
Asaia
in mosquitoes makes it a potential candidate for paratrangenic control in
Anopheles
. To better understand whether this bacterium could be used for malaria control, we quantified
Asaia
in
An. gambiae s.l
populations in malaria endemic regions examining co-infection with
Plasmodium falciparum
. Adult
Anopheles
mosquitoes were collected across two different eco-geographical localities in Cameroon, during both the dry and wet seasons. DNA was extracted from whole individual mosquitoes, and real time-qPCR amplification of the
16S ribosomal
RNA was used to quantify
Asaia
in both
An. gambiae
and
An. coluzzii
samples. We also detected and quantified
P. falciparum
infection in the same mosquitoes. The density of
Asaia
was successfully quantified in a total of 864 field mosquitoes, comprising of 439
An. gambiae
from Bankeng and 424
An. coluzii
collected from Gounougou. Interestingly, a higher prevalence of
Asaia
in
An. gambiae
(88.3%) compared to
An. coluzzii
(80.9%) was observed. Moreover, the density of
Asaia
in both species was significantly affected by seasonal changes in the two localities. Furthermore, a significant difference between the infection densities of
Asaia
and the
Plasmodium
infection status in the two species was recorded. However, no correlation was observed between the number of
Asaia
and
P. falciparum
infections. This study provides evidence that naturally occurring
Asaia
infection is not correlated to
P. falciparum
development within
An. gambiae
and
An. coluzzii
. Nevertheless, further studies incorporating experimental infections are required to better investigate the correlation between
Anopheles
mosquitoes,
Asaia,
and
Plasmodium
.

IMPORTANCE

The symbiont
Asaia
has emerged as a promising candidate for paratransgenic control of malaria, but further analysis of its biology and genetics across Africa is necessary. In this study, we investigated and quantified the influence of
Asaia
in naturally infected
An. gambiae s.l
. populations with the malaria parasite
Plasmodium falciparum
. Genomic DNA was extracted from whole individual mosquitoes collected from two localities, and
Asaia
was quantified using real-time qPCR by amplification of the 16S ribosomal RNA gene. We also detected and quantified
Plasmodium falciparum
infection in the same mosquitoes and established the correlation between
Asaia
and
Plasmodium
coinfection. This study provides evidence that naturally occurring
Asaia
infection is not correlated with
P. falciparum
development within
An. gambiae
and
An. coluzzii
mosquitoes.
Genotypic and phylogeographic insights into a pre-epidemic variant of Wesselsbron virus detected in sylvatic
Aedes mcintoshi
from Semuliki Forest, Uganda
Authors: Eibner Georg Joachim , Graff Selina Laura , Hieke Christian , Ochieng James Robert , Kopp Anne , Drosten Christian , Lutwama Julius , Rwego Innocent Bidason , Junglen Sandra
Published: November 2024

Wesselsbron virus (WSLV) is a neglected mosquito-borne virus within the yellow fever subgroup in the genus
Orthoflavivirus
of the
Flaviviridae
family. Despite being primarily a veterinary pathogen able to cause stillbirths, congenital malformations, and mortality in ruminants, WSLV also infects humans, causing a usually self-limiting febrile illness, or may lead to neurological complications in rare cases. WSLV causes sporadic outbreaks in Southern Africa, but findings in mosquitoes from other African countries suggest a wider distribution. Here, we report the detection and isolation of WSLV from an
Aedes mcintoshi
mosquito collected in a pristine ecosystem within Semuliki National Park, western Uganda. The detected strain M5937-UG-2018 was impaired in infectivity, replication, and production of infectious particles in cell lines derived from different hosts compared to an epidemic reference strain, SA H177. Full-genome sequencing by next-generation sequencing from the mosquito homogenate revealed a maximum nucleotide identity of 98.1% to a WSLV isolate from a human sample collected in South Africa in 1996. M5937-UG-2018 grouped in phylogenetic analyses with strains from South Africa and Senegal. Reconstruction of the temporal and spatial dispersal of WSLV across Africa estimated a likely origin of WSLV in South Africa in the early 19th century and spread in Southern Africa in the following decades. Long-distance movement toward Western and Eastern Africa was modeled to have occurred in the early 21st century. However, displacing the origin of M5937-UG-2018 did not decrease the likelihood of the model supporting the hypothesis that WSLV is widely distributed in Africa.

IMPORTANCE

WSLV is a neglected mosquito-borne virus causing teratogenicity in ruminants and febrile illness in humans. WSLV is mainly endemic to Southern Africa, but findings in other regions suggest a wider distribution on the continent. Knowledge of the distribution of WSLV is impaired as differential diagnostics are rarely performed in livestock and humans presenting with symptoms compatible with WSLV infection. Our work investigating viral infections in mosquitoes from a remote tropical rainforest region demonstrates that WSLV is endemic in Uganda. The isolated virus was less infective and showed lower replication ability
in vitro
compared to an epidemic isolate from South Africa. Phylogeographic reconstruction of spatial and temporal movements, along with the displacement of the origin of the newly detected strain
,
suggests that WSLV may be widely distributed across Africa. Our data show that the geographic distribution of WSLV and its impact on human and animal health are likely underestimated.
The PdxR-PdxKU locus involved in vitamin B
6
salvage is important for group A streptococcal resistance to neutrophil killing and survival in human blood
Authors: Davis Sarah E. , Hart Meaghan T. , Braza Rezia Era D. , Perry Aolani A. , Vega Luis A. , Le Breton Yoann S. , McIver Kevin S.
Published: November 2024

Streptococcus pyogenes
(Group A
Streptococcus
, GAS) is a Gram-positive bacterium that inflicts both superficial and life-threatening diseases on its human host. Analysis of fitness using a transposon mutant library revealed that genes predicted to be involved in vitamin B
6
acquisition are associated with fitness in whole human blood. Vitamin B
6
is essential for all life and is important for many cellular functions. In several streptococcal species, it has been shown that mutants in B
6
acquisition exhibited reduced virulence phenotypes and were attenuated during infection. In GAS, B
6
acquisition is believed to be controlled by the
pdxR-pdxKU
locus, where PdxR is a positive regulator of
pdxKU
, which encodes for a B
6
-substrate kinase and permease, respectively. Mutants in the regulator (Δ
pdxR
) and salvage machinery (Δ
pdxKU
) both exhibited modest growth defects when grown in oxygenated conditions with limited vitamin B
6
precursors. ∆
pdxR
and ∆
pdxKU
mutants also exhibited an impaired ability to survive when challenged with whole human or mouse blood. This defect was characterized by reduced survival in the presence of human neutrophil-like HL60s, primary polymorphonuclear leukocytes, and antimicrobial peptide LL-37. Promoter analysis showed that PdxR is an autoregulator and activated
pdxKU
in the absence of B
6
. Interestingly, ∆
pdxR
and ∆
pdxKU
mutants were not attenuated in mouse models of infection, suggesting a species-specific impact on virulence. Overall, it appears that
pdxR-pdxKU
is associated with GAS vitamin B
6
metabolism as well as pathogen survival during encounters with the human innate immune system.

IMPORTANCE

Bacterial pathogens such as
Streptococcus pyogenes
(Group A
Streptococcus
, GAS) must be able to obtain needed nutrients in their human host. Vitamin B
6
or pyridoxal 5’ phosphate is essential for all life and is important for many cellular functions. In other streptococcal pathogens, B
6
acquisition has been shown to be important for their ability to cause disease. Here, we show that loss of the putative vitamin B
6
salvage pathway locus
pdxR-pdxKU
affects GAS pathogenesis when encountering innate immune responses from phagocytic neutrophils and antimicrobial peptides within the host.
pdxR-
pdxKU may contribute to oxygen tolerance through B
6
; however, there appear to be other mechanisms for salvaging vitamin B
6
. Overall,
pdxR-pdxKU
is associated with GAS resistance to the human innate immune response and oxygen tolerance and contributes modestly to B
6
metabolism.
Macronutrient concentrations in human milk beyond the first half year of lactation: a cohort study
Authors: Muts Jacqueline , Lukowski Juliette I A , Twisk Jos W R , Schoonderwoerd Anne , van Goudoever Johannes B , van Keulen Britt J , Van Den Akker Chris H P
Published: November 2024

Objective

Human milk composition is dynamic. While extensive research has focused on its macronutrient concentrations during the first 6 months of lactation, limited research exists for extended lactation periods. This study aims to examine the nutritional composition of human milk during these longer lactation phases.

Design

A retrospective longitudinal cohort study performed within the National Dutch Human Milk Bank.

Participants

We selected donors who had provided milk donations at least once after the 6-month postpartum mark.

Main outcome measures

The Miris Human Milk Analyser was used to analyse macronutrient concentrations in the milk samples. Linear mixed models were used for longitudinal analysis of these concentrations, factoring in time variables established for six sequential lactation periods.

Results

We analysed 820 milk samples from 86 women, collected between 5 weeks and 28 months postpartum. Initially, milk protein concentrations dropped over the first 8 months of lactation (diff = −0.19 g/dL, p<0.001) and stabilised between 8 and 18 months before increasing again by 0.21 (95% CI 0.06–0.21) g/dL. Carbohydrate concentrations remained steady throughout the study period. Fat concentrations were stable for the first 8 months but saw an increase afterwards. Post 18 months, the fat content saw a rise of 1.90 (95% CI 1.59–2.21) g/dL. The caloric density mirrored the pattern of the fat concentrations.

Conclusion

The nutritional content of human milk does not decrease after 6 months of lactation. Therefore, human milk banks may accept donations from mothers up to 2 years post-birth.
Giant paediatric thymoma and its tailored anaesthetic management
Authors: Nisar Abdullah , bin Zafar Syed Tashfain , Mistry Akbar , Mohammad Hamid
Published: November 2024

A toddler presented with significant weight loss and lethargy. His CT scan chest revealed a sizeable anterior mediastinal mass of 14.5×12.0×7.0 cm, resulting in compression of the airway. The patient underwent a successful tumour resection but postoperatively experienced left diaphragmatic paralysis, which was effectively managed through conservative measures. Histopathology was consistent with thymoma (type B2, Masaoka stage I). This case emphasises the critical role of collaborative efforts among oncology, surgery and anaesthesiology teams in achieving positive outcomes for rare paediatric mediastinal tumours. It underscores the importance of comprehensive preoperative anaesthetic assessments, careful planning for potential complications and vigilant postoperative monitoring. Healthcare professionals, particularly anaesthesiologists, can find valuable insights in this case report for navigating the complexities associated with managing giant mediastinal masses in the paediatric population.
Beyond Seizures: the enigma of cardioinhibitory malignant vasovagal syncope in a complicated pregnancy journey
Authors: Sierra Juan G , Rojo Laura , Gonzalez Reyes Laura , Boccalandro Fernando
Published: November 2024

A pregnant woman in her late 20s with a history of epilepsy since childhood presented with recurrent loss of consciousness and witnessed twitching and involuntary muscle contractions. She had hyperemesis during pregnancy reporting four previous miscarriages attributed to seizures. During evaluation in cardiac telemetry and while suffering from severe nausea, the patient experienced prolonged ventricular asystole resulting in convulsive syncope and was diagnosed with cardioinhibitory malignant vasovagal syncope (CMVS). Initiation of levetiracetam was recommended for 6 months, and after undergoing dual-chamber pacemaker placement, her neurological symptoms resolved despite persistent hyperemesis during the first trimester, leading to a successful vaginal delivery. 4 years later, the patient remains asymptomatic. This case emphasises the importance of conducting a thorough differential diagnosis in patients with atypical seizure presentations, the multidisciplinary approach required to assure optimal outcomes in cardio-obstetric cases and the role of selective pacemaker placement in patients with documented prolonged ventricular asystole associated with CMVS.
(Intravascular) papillary endothelial hyperplasia or Masson’s tumour of the axilla in a patient with a history of breast cancer
Authors: Van Houdt Maxime , Fidlers Tom , Neven Patrick , Han Sileny
Published: November 2024

Intravascular papillary endothelial hyperplasia, or Masson’s tumour, is a benign lesion of the subcutaneous tissue and skin, characterised by a reactive proliferation of endothelial cells within a vessel. Although this pathology can occur at various sites, it is generally rare. Differential diagnosis with other benign lesions or malignancies can be challenging, and since its circumscribed nature is impossible to recognise with a biopsy, excision is frequently required.

We present the case of a female patient with a history of bilateral breast cancer, treated with surgery, chemotherapy and radiotherapy, who developed a slowly growing, large bulging mass in the right axilla. Biopsies were benign, and the positron emission tomography–CT showed no hypermetabolism of the mass. However, due to the debilitating bleeding from the fragile mass and uncertainty about its biological behaviour, excision was performed. Pathological examination revealed an intravascular lesion with a central thrombus, characteristic of intravascular papillary endothelial hyperplasia.
Curious phenomenon of ‘hook effect’ in invasive mole
Authors: Heda Sakshi , Fuke Rujuta , Heda Ayush , Gattani Preeti
Published: November 2024

Gestational trophoblastic disease is a group of pregnancy-related trophoblastic tumours. Gestational trophoblastic neoplasia refers to its invasive and malignant forms: invasive mole, choriocarcinoma, placental site trophoblastic tumour and epithelioid trophoblastic tumour. Patients exhibit elevated beta human chorionic gonadotropin (β hCG) levels, sometimes exceeding 100 000 mIU/mL. When the serum levels of hCG surpass 500 000 mIU/mL, there is a possibility of encountering a phenomenon called ‘hook effect’ which causes erroneously low or negative value when using the immunometric hCG assays that are presently available in the commercial market. We present a rare case involving a female in mid-30s with an invasive molar pregnancy presenting with bleeding, an abdominal mass, hypertension and hyperthyroidism. Despite a negative urine β hCG test, her serum hCG, after dilution, was recalculated to over 850 000 mIU/mL. MRI confirmed invasive mole. Post-hysterectomy, she received methotrexate chemotherapy. Her β hCG normalised after two cycles, and she remains disease-free for 14 months.
Recurrent femoral neck fractures: keep an eye out for Cushing’s syndrome
Authors: Alam Ahmad , Patra Shinjan , Agrawal Neeraj Kumar , Singh Surya K
Published: November 2024

Prolonged glucocorticoid overexposure leads to Cushing’s syndrome (CS). It is characterised by diverse metabolic, cardiovascular and bone mineral manifestations. A middle-aged woman presented for a preoperative evaluation of a pathological fracture of the left neck of the femur. She had a history of a hip fracture on the opposite side 3 years back. She exhibited several features specific to CS and was subsequently diagnosed with Cushing’s disease. She underwent transsphenoidal adenoma resection and achieved remission. Glucocorticoids primarily affect the trabecular bone compared with cortical bones, and vertebral fractures are common in CS. The femoral neck consists of both trabecular and cortical bone and can be involved in CS. Our patient was not diagnosed as CS at the first pathological fracture and was subsequently diagnosed only after the second fracture. This case report underscores the importance of a diligent search for a possible endocrinological aetiology in any case of pathological fractures.
Detailed primary localised cutaneous nodular amyloidosis clinical and pathological workup
Authors: Ayub Mahaa , Kaminoff Lizabeth , Maity Alisha , Ali Zonera
Published: November 2024

Primary localised cutaneous nodular amyloidosis is a rare form of amyloidosis characterised by amyloid deposition in the skin but a lack of further organ involvement; therefore, it is not a systemic disease that progresses to complication. Limited knowledge exists on the causes and outcomes of long-term cutaneous nodular amyloidosis patients. This study reports a case of a woman in her late 80s presenting with a primary cutaneous nodular amyloidosis, with yellow, white plaques and a focal area of violaceous nodules along the inferior lumbar spine. Notably, this rash has been present for nearly 40 years. Histopathological examination revealed amyloid deposits, but further examination showed no amyloid systemic involvement. Recognition of primary nodular amyloidosis through skin biopsy is essential, and current clinical recommendations are to perform pathology examinations to make the diagnosis.
Identifying important and feasible primary care structures and processes in the US healthcare system: a modified Delphi study
Authors: Albert Stephanie L , Kwok Lorraine , Shelley Donna R , Paul Maggie M , Blecker Saul B , Nguyen Ann M , Harel Daphna , Cleland Charles M , Weiner Bryan J , Cohen Deborah J , Damschroder Laura , Berry Carolyn A
Published: November 2024

Objective

To identify primary care structures and processes that have the highest and lowest impact on chronic disease management and screening and prevention outcomes as well as to assess the feasibility of implementing these structures and processes into practice.

Design

A two-round Delphi study was conducted to establish consensus on the impact and feasibility of 258 primary care structures and processes.

Participants

29 primary care providers, health system leaders and health services researchers in the USA.

Outcomes

Primary outcomes were (1) consensus on the impact of each structure and process on chronic disease management and screening and prevention outcomes, separately and (2) consensus on feasibility of implementation by primary care practices.

Results

Consensus on high impact and feasibility of implementation was reached on four items for chronic disease management: ‘Providers use motivational interviewing to help patients set goals’, ‘Practice has designated staff to manage patient panel’, ‘Practice has onsite providers or staff that speak the most dominant, non-English language spoken by patients’ and ‘Practice includes mental health providers and/or behavioural health specialists in care team’ and seven items for screening and prevention: ‘Practice utilizes standing protocols and orders’, ‘Practice generates reports to alert clinicians to missed targets and to identify gaps in care, such as overdue visits, needed vaccinations, screenings or other preventive services’, ‘Practice has designated staff to manage patient panel’, ‘Practice sets performance goals and uses benchmarking to track quality of care’, ‘Practice uses performance feedback to identify practice-specific areas of improvement’, ‘Practice builds quality improvement activities into practice operations’ and ‘Pre-visit planning data are reviewed during daily huddles’. Only ‘Practice has designated staff to manage patient panel’ appeared on both lists.

Conclusion

Findings suggest that practices need to focus on implementing mostly distinct, rather than common, structures and processes to optimise chronic disease and preventive care.