bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish
Authors: Zhang Chengting , Brunt Lucy , Ono Yosuke , Rogers Sally , Scholpp Steffen 
Published: December 2023

AbstractChemical signalling is the primary means by which cells communicate in the embryo. The underlying principle refers to a group of ligand-producing cells and a group of cells that respond to this signal because they express the appropriate receptors1,2. In the zebrafish embryo, Wnt5b binds to the receptor Ror2 to trigger the Wnt–planar cell polarity (PCP) signalling pathway to regulate tissue polarity and cell migration3,4. However, it remains unclear how this lipophilic ligand is transported from the source cells through the aqueous extracellular space to the target tissue. In this study, we provide evidence that Wnt5b, together with Ror2, is loaded on long protrusions called cytonemes. Our data further suggest that the active Wnt5b–Ror2 complexes form in the producing cell and are handed over from these cytonemes to the receiving cell. Then, the receiving cell has the capacity to initiate Wnt–PCP signalling, irrespective of its functional Ror2 receptor status. On the tissue level, we further show that cytoneme-dependent spreading of active Wnt5b–Ror2 affects convergence and extension in the zebrafish gastrula. We suggest that cytoneme-mediated transfer of ligand–receptor complexes is a vital mechanism for paracrine signalling. This may prompt a reevaluation of the conventional concept of characterizing responsive and non-responsive tissues solely on the basis of the expression of receptors.
The PfRCR complex bridges malaria parasite and erythrocyte during invasion
Authors: Farrell Brendan , Alam Nawsad , Hart Melissa N. , Jamwal Abhishek , Ragotte Robert J. , Walters-Morgan Hannah , Draper Simon J. , Knuepfer Ellen , Higgins Matthew K. 
Published: December 2023

AbstractThe symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex1, containing PfRH5 (refs. 2,3), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies3–6 or nanobodies1 against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex7,8, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane9, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies5 neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies6, binds to the PfCSS–PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design.
Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes
Authors: Moschandrea Chrysanthi , Kondylis Vangelis , Evangelakos Ioannis , Herholz Marija , Schneider Farina , Schmidt Christina , Yang Ming , Ehret Sandra , Heine Markus , Jaeckstein Michelle Y. , Szczepanowska Karolina , Schwarzer Robin , Baumann Linda , Bock Theresa , Nikitopoulou Efterpi , Brodesser Susanne , Krüger Marcus , Frezza Christian , Heeren Joerg , Trifunovic Aleksandra , Pasparakis Manolis 
Published: December 2023

AbstractDigested dietary fats are taken up by enterocytes where they are assembled into pre-chylomicrons in the endoplasmic reticulum followed by transport to the Golgi for maturation and subsequent secretion to the circulation1. The role of mitochondria in dietary lipid processing is unclear. Here we show that mitochondrial dysfunction in enterocytes inhibits chylomicron production and the transport of dietary lipids to peripheral organs. Mice with specific ablation of the mitochondrial aspartyl-tRNA synthetase DARS2 (ref. 2), the respiratory chain subunit SDHA3 or the assembly factor COX10 (ref. 4) in intestinal epithelial cells showed accumulation of large lipid droplets (LDs) in enterocytes of the proximal small intestine and failed to thrive. Feeding a fat-free diet suppressed the build-up of LDs in DARS2-deficient enterocytes, which shows that the accumulating lipids derive mostly from digested fat. Furthermore, metabolic tracing studies revealed an impaired transport of dietary lipids to peripheral organs in mice lacking DARS2 in intestinal epithelial cells. DARS2 deficiency caused a distinct lack of mature chylomicrons concomitant with a progressive dispersal of the Golgi apparatus in proximal enterocytes. This finding suggests that mitochondrial dysfunction results in impaired trafficking of chylomicrons from the endoplasmic reticulum to the Golgi, which in turn leads to storage of dietary lipids in large cytoplasmic LDs. Taken together, these results reveal a role for mitochondria in dietary lipid transport in enterocytes, which might be relevant for understanding the intestinal defects observed in patients with mitochondrial disorders5.
Minute-scale oscillatory sequences in medial entorhinal cortex
Authors: Gonzalo Cogno Soledad , Obenhaus Horst A. , Lautrup Ane , Jacobsen R. Irene , Clopath Claudia , Andersson Sebastian O. , Donato Flavio , Moser May-Britt , Moser Edvard I. 
Published: December 2023

AbstractThe medial entorhinal cortex (MEC) hosts many of the brain’s circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. Whereas location is known to be encoded by spatially tuned cell types in this brain region2,3, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.
Emergence of replication timing during early mammalian development
Authors: Nakatani Tsunetoshi , Schauer Tamas , Altamirano-Pacheco Luis , Klein Kyle N. , Ettinger Andreas , Pal Mrinmoy , Gilbert David M. , Torres-Padilla Maria-Elena 
Published: December 2023

AbstractDNA replication enables genetic inheritance across the kingdoms of life. Replication occurs with a defined temporal order known as the replication timing (RT) programme, leading to organization of the genome into early- or late-replicating regions. RT is cell-type specific, is tightly linked to the three-dimensional nuclear organization of the genome1,2 and is considered an epigenetic fingerprint3. In spite of its importance in maintaining the epigenome4, the developmental regulation of RT in mammals in vivo has not been explored. Here, using single-cell Repli-seq5, we generated genome-wide RT maps of mouse embryos from the zygote to the blastocyst stage. Our data show that RT is initially not well defined but becomes defined progressively from the 4-cell stage, coinciding with strengthening of the A and B compartments. We show that transcription contributes to the precision of the RT programme and that the difference in RT between the A and B compartments depends on RNA polymerase II at zygotic genome activation. Our data indicate that the establishment of nuclear organization precedes the acquisition of defined RT features and primes the partitioning of the genome into early- and late-replicating domains. Our work sheds light on the establishment of the epigenome at the beginning of mammalian development and reveals the organizing principles of genome organization.
Sudden death in young South European population: a cross-sectional study of postmortem cases
Authors: Carrington Mafalda , de Gouveia Rosa Henriques , Teixeira Rogério , Corte-Real Francisco , Gonçalves Lino , Providência Rui 
Published: December 2023

AbstractTo describe the annual incidence and the leading causes of sudden non-cardiac and cardiac death (SCD) in children and young adult Portuguese population. We retrospectively reviewed autopsy of sudden unexpected deaths reports from the Portuguese National Institute of Legal Medicine and Forensic Sciences’ database, between 2012 and 2016, for the central region of Portugal, Azores and Madeira (ages 1–40: 26% of the total population). During a 5-year period, 159 SD were identified, corresponding to an annual incidence of 2,4 (95%confidence interval, 1,5–3,6) per 100.000 people-years. Victims had a mean age of 32 ± 7 years-old, and 72,3% were male. There were 70,4% cardiac, 16,4% respiratory and 7,5% neurologic causes of SD. The most frequent cardiac anatomopathological diagnosis was atherosclerotic coronary artery disease (CAD) (33,0%). There were 15,2% victims with left ventricular hypertrophy, with a diagnosis of hypertrophic cardiomyopathy only possible in 2,7%. The prevalence of cardiac pathological findings of uncertain significance was 30,4%. In conclusion, the annual incidence of SD was low. Atherosclerotic CAD was diagnosed in 33,0% victims, suggesting the need to intensify primary prevention measures in the young. The high prevalence of pathological findings of uncertain significance emphasizes the importance of molecular autopsy and screening of first-degree relatives.
Psychological distress and voting behaviour in nine countries of the former Soviet Union
Authors: Stickley Andrew , Sumiyoshi Tomiki , Kondo Naoki , Leinsalu Mall , Inoue Yosuke , Ruchkin Vladislav , Shin Jae Il , McKee Martin 
Published: December 2023

AbstractPoorer mental health is linked to a lower likelihood of voting in elections. However, little is known about this association in non-Western settings. This study examined the association between psychological distress and voting in nine countries of the former Soviet Union (FSU). Data were analysed from 18,000 respondents aged ≥ 18 in Armenia, Azerbaijan, Belarus, Georgia, Moldova, Kazakhstan, Kyrgyzstan, Russia and Ukraine collected during the Health in Times of Transition (HITT) survey in 2010/11. Information was collected on previous voting behaviour and future voting intentions. Psychological distress was assessed with a 12-item scale. In pooled multivariable logistic regression analyses psychological distress was significantly associated with ‘never voting’ (not having voted previously or intending to vote in future) and ‘past voting only’ (having voted previously but not intending to vote in future). In stratified analyses psychological distress was linked to never voting in women and working-age adults. The significant association between psychological distress and voting was observed only in hybrid political regimes. Psychological distress is associated with a reduced likelihood of voting in FSU countries especially among women, working-age adults and those in hybrid political regimes.
Preparation and characterization of a curcumin nanoemulsion gel for the effective treatment of mycoses
Authors: Al Fatease Adel , Alqahtani Ali , Khan Barkat A. , Mohamed Jamal Moideen Muthu , Farhana Syeda Ayesha 
Published: December 2023

AbstractFungal infections of skin including mycoses are one of the most common infections in skin or skins. Mycosis is caused by dermatophytes, non-dermatophyte moulds and yeasts. Various studies show different drugs to treat mycoses, yet there is need to treat it with applied drugs delivery. This study was designed to prepare a bio curcumin (CMN) nanoemulsion (CMN-NEs) for transdermal administration to treat mycoses. The self-nanoemulsification approach was used to prepare a nanoemulsion (NE), utilizing an oil phase consisting of Cremophor EL 100 (Cre EL), glyceryl monooleate (GMO), and polyethylene glycol 5000 (PEG 5000). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), Fourier transform infrared (FTIR) spectrophotometric analysis, and morphological analyses were performed to evaluate the nanoemulsion (NE). The in vitro permeation of CMN was investigated using a modified vertical diffusion cell with an activated dialysis membrane bag. Among all the formulations, a stable, spontaneously produced nanoemulsion was determined with 250 mg of CMN loaded with 10 g of the oil phase. The average droplet size, ZP, and PDI of CMN-NEs were 90.0 ± 2.1 nm, − 7.4 ± 0.4, and 0.171 ± 0.03 mV, respectively. The release kinetics of CMN differed from zero order with a Higuchi release profile as a result of nanoemulsification, which also significantly increased the flux of CMN permeating from the hydrophilic matrix gel. Overall, the prepared nanoemulsion system not only increased the permeability of CMN but also protected it against chemical deterioration. Both CMN-ME (24.0 ± 0.31 mm) and CMN-NE gel (29.6 ± 0.25 mm) had zones of inhibition against Candida albicans that were significantly larger than those of marketed Itrostred gel (21.5 ± 0.34 mm). The prepared CMN-NE improved the bioavailability, better skin penetration, and the CMN-NE gel enhanced the release of CMN from the gel matrix on mycotic patients.
Association between reduced left ventricular ejection fraction and peritoneal dialysis related peritonitis: a single center retrospective cohort study in Japan
Authors: Yamaguchi Makoto , Obayashi Takaaki , Kobayashi Naoto , Izumi Naoki , Nagai Masaaki , Nobata Hironobu , Asai Akimasa , Kamiya Keisuke , Sugiyama Hirokazu , Kinashi Hiroshi , Banno Shogo , Ando Masahiko , Imaizumi Takahiro , Kubo Yoko , Katsuno Takayuki , Ishimoto Takuji , Ito Yasuhiko 
Published: December 2023

AbstractWe present a single-center retrospective analysis of 228 Japanese patients with peritoneal dialysis, in which we examined whether reduced left ventricular ejection fraction (LVEF) is a risk factor for peritonitis development. Time-dependent multivariable-adjusted Cox proportional hazards models revealed that reduced LVEF (LVEF < 50% vs. preserved LVEF ≥ 50%, hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.16–3.82) was associated with peritonitis. Qualitatively, similar associations with reduced LVEF (< 50%) were observed for enteric peritonitis (adjusted HR 7.68; 95% CI 2.51–23.5) but not for non-enteric peritonitis (adjusted HR 1.15; 95% CI 0.54–2.44). Reduced LVEF is associated with a significantly higher risk of subsequent peritonitis, particularly enteric peritonitis. These results indicate that patients with reduced LVEF may be at risk of enteric peritonitis from bowel sources caused by intestinal involvement due to cardiac dysfunction.
Analysis of factors associated with delayed diagnosis and treatment of testicular torsion in 1005 cases from Chongqing city, China: a cross-sectional study
Authors: Yi Hongmei , Wang Delin , Wu Xiaohou , Gan Xiangzhi , Wang Dan , zhao Xin , Cheng Honglin 
Published: December 2023

AbstractThis study aimed to investigate the clinical and social factors of delayed treatment for testicular torsion (TT) and to explore the risk factors of testicular excision in China. The clinical data of 1005 patients with TT who were admitted to 48 medical institutions in Chongqing city (China) from January 2012 to December 2021 were retrospectively analyzed. It was revealed that the misdiagnosis rates of non-senior (junior and middle) grade doctors and senior doctors were 25.1% and 9.6%, respectively. The proportion of TT patients who received timely treatment (within 6 h after onset of symptoms) was 23.8%. The results of the multivariable logistic regression analysis indicated that absent cremasteric reflex was a protective factor for delayed surgery of more than 6 h from onset of symptoms to surgery. Misdiagnosis, consultation with a non-urologist as the first consultant doctor, absence blood flow in color Doppler ultrasound, negative high-riding testis findings, the presence of fever, and non-manual detorsion were identified as risk factors associated with delayed surgery (more than 6 h from the onset of symptoms) for TT. Furthermore, misdiagnosis, non-urologist first-consultant doctor, absent blood flow in DUS, non-manual detorsion, fever, degree of cord twisting > 180, and the initial diagnosis in tertiary hospitals were risk factors for orchidectomy. Having TT on the right side, and the presence of nausea and vomiting were identified as protective factors for orchidectomy. Technical training in the diagnosis and treatment of TT should be extended to primary hospitals and doctors to significantly improve their accuracy in managing this condition.
A neural network computational structure for the fractional order breast cancer model
Authors: Huang Zhenglin , Haider Qusain , Sabir Zulqurnain , Arshad Mubashar , Siddiqui Bushra Khatoon , Alam Mohammad Mahtab 
Published: December 2023

AbstractThe current study provides the numerical performances of the fractional kind of breast cancer (FKBC) model, which are based on five different classes including cancer stem cells, healthy cells, tumor cells, excess estrogen, and immune cells. The motive to introduce the fractional order derivatives is to present more precise solutions as compared to integer order. A stochastic computing reliable scheme based on the Levenberg Marquardt backpropagation neural networks (LMBNNS) is proposed to solve three different cases of the fractional order values of the FKBC model. A designed dataset is constructed by using the Adam solver in order to reduce the mean square error by taking the data performances as 9% for both testing and validation, while 82% is used for training. The correctness of the solver is approved through the negligible absolute error and matching of the solutions for each model’s case. To validates the accuracy, and consistency of the solver, the performances based on the error histogram, transition state, and regression for solving the FKBC model.
Safety of using a large femoral head on thin polyethylene for total hip arthroplasty based on different types of polyethylene
Authors: Do Min Uk , Moon Nam Hoon , Suh Kuen Tak , Kim Jung Shin , Lee Sang-Min , Shin Won Chul 
Published: December 2023

AbstractThe use of a large femoral head in total hip arthroplasty (THA) to stabilize and reduce the incidence of dislocation is on the increase, but concerns arise when combining them with small acetabular components due to potential mechanical failures in thin polyethylene (PE) liners. A single-institution, retrospective cohort study was conducted on 116 patients with minimum 2-year follow-up who received 36-mm femoral heads and acetabular components ≤ 52 mm, using either remelted highly cross-linked polyethylene (remelted HXLPE) or vitamin E-infused HXLPE (VEPE). Osteolysis and implant loosening were not observed in either group. Although a fracture of the PE liner was observed in each group (1.7%), the clinical outcomes were excellent, as the mean modified Harris Hip Score (mHHS) at the last follow-up was 93.5. Moreover, the mean linear wear rates measured by digital imaging software in both groups were low, with 0.035 mm/y in remelted HXLPE and 0.030 mm/y in VEPE. In conclusion, The use of a large femoral head on a thin PE liner can be a viable treatment option in patients who need to prioritize stability; however, careful attention should be paid to mechanical fractures of the PE liner.
Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia
Authors: Nishino Reiko , Nomura-Komoike Kaori , Iida Tomohiro , Fujieda Hiroki 
Published: December 2023

AbstractRetinal Müller glia have a capacity to regenerate neurons in lower vertebrates like zebrafish, but such ability is extremely limited in mammals. In zebrafish, Müller glia proliferate after injury, which promotes their neurogenic reprogramming while inhibiting reactive gliosis. In mammals, however, how the cell cycle affects the fate of Müller glia after injury remains unclear. Here, we focused on the expression of proneural transcription factors, Ngn2 and Ascl1, and a gliosis marker glial fibrillary acidic protein (GFAP) in rat Müller glia after N-methyl-N-nitrosourea (MNU)-induced photoreceptor injury and analyzed the role of Müller glia proliferation in the regulation of their expression using retinal explant cultures. Thymidine-induced G1/S arrest of Müller glia proliferation significantly hampered the expression of Ascl1, Ngn2, and GFAP, and release from the arrest induced their upregulation. The migration of Müller glia nuclei into the outer nuclear layer was also shown to be cell cycle-dependent. These data suggest that, unlike the situation in zebrafish, cell cycle progression of Müller glia in mammals promotes both neurogenic reprogramming and reactive gliosis, which may be one of the mechanisms underlying the limited regenerative capacity of the mammalian retina.
Impact of long COVID on the heart rate variability at rest and during deep breathing maneuver
Authors: da Silva Andréa Lúcia Gonçalves , Vieira Luana dos Passos , Dias Luiza Scheffer , Prestes Cecília Vieira , Back Guilherme Dionir , Goulart Cassia da Luz , Arena Ross , Borghi-Silva Audrey , Trimer Renata 
Published: December 2023

AbstractWhile the majority of individuals with coronavirus disease 2019 (COVID-19) recover completely, a significant percentage experience persistent symptom, which has been characterized as Long COVID and may be associated with cardiac and autonomic dysfunction. We evaluated heart rate variability (HRV) at rest and during deep-breathing (M-RSA) in patients with Long COVID. Case–control design involved 21 patients with Long COVID and 20 controls; the HRV was evaluated (POLAR system) at rest in the supine position and during M-RSA and expressed in time domain and non-linear analysis. In the supine position we found a reduction HRV measures in Long COVID’ patients compared to controls for: Mean_iRR (p < 0.001), STD_iRR (p < 0.001); STD_HR (p < 0.001); SD1 (p < 0.001); SD2 (p < 0.001); alpha2 (p < 0.001). In the M-RSA we found reduction Mean_iRR (p < 0.001), STD_iRR (p < 0.001), STD_HR (p < 0.001), rMSSD (p < 0.001), RR_tri-index (p < 0.001) in Long COVID’ patients except for highest Mean_HR p < 0.001. In conclusion, Long COVID reduced HRV at rest and during deep breathing. These findings may imply impairment of cardiac autonomic control when symptoms of COVID-19 persist following initial recovery.