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1.
PLoS Negl Trop Dis ; 18(9): e0012458, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39236074

RESUMEN

Phlebotomine sand flies are vectors of the protozoan parasite Leishmania spp. Although the intestinal microbiota is involved in a wide range of biological and physiological processes and has the potential to alter vector competence, little is known about the impact of host species and environment on the gut microbiome. To address this issue, a comparative analysis of the microbiota of sand fly vector populations of Leishmania major and L. tropica in a mixed focus of cutaneous leishmaniasis in Tunisia was performed. Bacterial 16S rRNA gene amplification and Illumina MiSeq sequencing were used to characterize and compare the overall bacterial and fungal composition of field-collected sand flies: Phlebotomus papatasi, Ph. perniciosus, Ph. riouxi, and Ph. sergenti. Thirty-eight bacterial genera belonging to five phyla were identified in 117 female specimens. The similarities and differences between the microbiome data from different samples collected from three collections were determined using principal coordinate analysis (PCoA). Substantial variations in the bacterial composition were found between geographically distinct populations of the same sand fly species, but not between different species at the same location, suggesting that the microbiota content was structured according to environmental factors rather than host species. These findings suggest that host phylogeny may play a minor role in determining the insect gut microbiota, and its potential to affect the transmission of the Leishmania parasite appear to be very low. These results highlight the need for further studies to decode sand fly Leishmania-microbiota interactions, as even the same bacterial species, such as Enterococcus faecalis, can exert completely opposite effects when confronted with different pathogens within various host insects and vice versa.


Asunto(s)
Bacterias , Insectos Vectores , Leishmania major , Leishmania tropica , Leishmaniasis Cutánea , Animales , Túnez , Leishmania major/genética , Leishmania major/aislamiento & purificación , Leishmaniasis Cutánea/transmisión , Leishmaniasis Cutánea/microbiología , Leishmaniasis Cutánea/parasitología , Insectos Vectores/microbiología , Insectos Vectores/parasitología , Leishmania tropica/genética , Leishmania tropica/aislamiento & purificación , Femenino , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , ARN Ribosómico 16S/genética , Microbiota , Psychodidae/microbiología , Psychodidae/parasitología , Phlebotomus/microbiología , Phlebotomus/parasitología , Filogenia , Microbioma Gastrointestinal
2.
Surg Case Rep ; 10(1): 217, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259237

RESUMEN

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare malignant gastrointestinal tumor. The prognosis of patients with MiNEN is poor because of the high frequency of recurrence and metastases. We report a case of esophagogastric junction MiNEN (EGJ-MiNEN) with a long-term recurrence-free survival of 5.5 years. CASE PRESENTATION: A 58-year-old male patient underwent thoracoscopic esophagectomy for esophagogastric junction adenocarcinoma. The patient's postoperative course was uneventful. R0 resection was achieved, and the pathological diagnosis of the surgical specimen was pT3N2M0 Stage IIIA (according to the Japanese Classification of Gastric Cancer, 4th edition). Based on the pathology results, the patient was treated with postoperative adjuvant therapy with oral S-1. The patient maintained recurrence-free survival for 5.5 years postoperatively. However, 6 years postoperatively, the patient visited our department with cachexia. Computed tomography (CT) revealed a large amount of ascites and pleural effusion. He rapidly developed a poor circulatory and respiratory status and died 16 days after admission. An autopsy revealed severe bloody ascites and pleural effusion, as well as numerous nodules on the pleura and mesentery. Immunohistochemistry of the nodules revealed positivity for chromogranin A, Synaptophysin A, neural cell adhesion molecule (NCAM or CD56), and insulinoma-associated protein 1 (INSM1). The specimen showed a mixture of adenocarcinoma and neuroendocrine cell carcinoma and was diagnosed as MiNEN. Retrospective immunostaining of the surgical specimen showed similar results, and we diagnosed the patient with recurrence of EGJ-MiNEN. CONCLUSION: MiNEN has a poor prognosis; however, in some cases, long-term recurrence-free survival is achieved with radical resection and adjuvant chemotherapy.

3.
J Neurosurg Case Lessons ; 8(8)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39159492

RESUMEN

BACKGROUND: Craniotomy is required for the removal of brainstem cavernous malformations (CMs) with repeated hemorrhage, and this condition is often complicated by an accompanying developmental venous anomaly (DVA). However, a DVA of the brainstem or cerebellum with drainage penetrating the pons is an exceptional finding. OBSERVATIONS: A 57-year-old man presented with double vision. Computed tomography revealed progressive enlargement of the hemorrhage in the dorsal pons. Contrast-enhanced magnetic resonance angiography revealed an expanded transverse vessel penetrating the center of the pons in contact with the CM. Digital subtraction angiography revealed that the DVA, comprising the expanded transpontine vein and some cerebellar medullary veins acting as normal venous drainage, coexisted with the CM. By utilizing the angioarchitecture and intraoperative neuronavigation system data, electrophysiological mapping, and indocyanine green videoangiography, complete removal of the CM was accomplished while preserving the DVA and brain function. LESSONS: This study presents the intraoperative images of an expanded transpontine vein as a DVA, which has never been depicted in a live patient before, accompanied by a CM in the dorsal portion of the pons. https://thejns.org/doi/10.3171/CASE24314.

4.
G3 (Bethesda) ; 14(9)2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39031588

RESUMEN

Drosophila subobscura is distributed across Europe, the Near East, and the Americas, while its sister species, Drosophila madeirensis, is endemic to the island of Madeira in the Atlantic Ocean. D. subobscura is known for its strict light-dependence in mating and its unique courtship displays, including nuptial gift-giving. D. subobscura has also attracted the interest of researchers because of its abundant variations in chromosomal polymorphisms correlated to the latitude and season, which have been used as a tool to track global climate warming. Although D. madeirensis can be an important resource for understanding the evolutionary underpinning of these genetic characteristics of D. subobscura, little work has been done on the biology of this species. Here, we used a HiFi long-read sequencing data set to produce a de novo genome assembly for D. madeirensis. This assembly comprises a total of 111 contigs spanning 135.5 Mb and has an N50 of 24.2 Mb and a BUSCO completeness score of 98.6%. Each of the 6 chromosomes of D. madeirensis consisted of a single contig except for some centromeric regions. Breakpoints of the chromosomal inversions between D. subobscura and D. madeirensis were characterized using this genome assembly, updating some of the previously identified locations.


Asunto(s)
Cromosomas de Insectos , Drosophila , Genoma de los Insectos , Animales , Drosophila/genética , Cromosomas de Insectos/genética , Genómica/métodos , Anotación de Secuencia Molecular , Islas
5.
Intern Med ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38987194

RESUMEN

Autoimmune neuromuscular disorders in patients with eosinophilic granulomatosis with polyangiitis (EGPA) are relatively uncommon. Although two cases of myasthenia gravis (MG) comorbid with EGPA have been reported, both patients developed EGPA several years after starting immunosuppressive treatment for MG. We herein report a 75-year-old man with a rare co-occurrence of EGPA and MG that developed simultaneously and was successfully treated with immunosuppressive therapy. Distinguishing the neurological symptoms of EGPA from complications of other neurological autoimmune diseases, such as MG, is crucial, especially in patients with eosinophilia.

6.
Phys Rev Lett ; 132(21): 213401, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38856247

RESUMEN

An advanced cooling scheme, incorporating entropy engineering, is vital for isolated artificial quantum systems designed to emulate the low-temperature physics of strongly correlated electron systems. This study theoretically demonstrates a cooling method employing multicomponent Fermi gases with SU(N)-symmetric interactions, focusing on the case of ^{173}Yb atoms in a two-dimensional optical lattice. Adiabatically introducing a nonuniform state-selective laser gives rise to two distinct subsystems: a central low-entropy region, exclusively composed of two specific spin components, acts as a quantum simulator for strongly correlated electron systems, while the surrounding N-component mixture retains a significant portion of the entropy of the system. The total particle numbers for each component are good quantum numbers, creating a sharp boundary for the two-component region. The cooling efficiency is assessed through extensive finite-temperature Lanczos calculations. The results lay the foundation for quantum simulations of two-dimensional systems of Hubbard or Heisenberg type, offering crucial insights into intriguing low-temperature phenomena in condensed-matter physics.

7.
J Biochem ; 176(3): 187-195, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38889670

RESUMEN

Intratumour heterogeneity has been shown to play a role in the malignant progression of cancer. The clonal evolution in primary cancer has been well studied, however, that in metastatic tumorigenesis is not fully understood. In this study, we established human colon cancer-derived organoids and investigated clonal dynamics during liver metastasis development by tracking barcode-labelled subclones. Long-term subclone co-cultures showed clonal drift, with a single subclone becoming dominant in the cell population. Interestingly, the selected subclones were not always the same, suggesting that clonal selection was not based on cell intrinsic properties. Furthermore, liver tumours developed by co-transplantation of organoid subclones into the immunodeficient mouse spleen showed a progressive drastic reduction in clonal diversity, and only one or two subclones predominated in the majority of large metastatic tumours. Importantly, selections were not limited to particular subclones but appeared to be random. A trend towards a reduction in clonal diversity was also found in liver metastases of multiple colour-labelled organoids of mouse intestinal tumours. Based on these results, we propose a novel mechanism of metastasis development, i.e. a subclone population of the disseminated tumour cells in the liver is selected by neutral selection during colonization and constitutes large metastatic tumours.


Asunto(s)
Neoplasias del Colon , Neoplasias Hepáticas , Neoplasias del Colon/patología , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Humanos , Animales , Ratones , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Organoides/patología , Organoides/metabolismo , Metástasis de la Neoplasia , Evolución Clonal
8.
Clin Nutr ESPEN ; 61: 295-301, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38777447

RESUMEN

BACKGROUND & AIMS: Track and field sprinters must obtain an optimal body composition to improve sprint performance. To successfully change body composition, it is important to evaluate the estimated energy requirements (EER) and fluctuations in total energy expenditure (TEE). However, methods to accurately evaluate the EER and TEE in sprinters have not been fully investigated. The aim of this study was to compare currently used methods with the doubly labeled water (DLW) method, which is currently the gold standard for evaluating EER and TEE. METHODS: Ten male collegiate sprinters participated in the study. We evaluated TEEDLW and compared it with the EER calculated using two equations used by the National Institute of Health and Nutrition (NIHN) and the Japan Institute of Sports Sciences (JISS). In addition, we evaluated the TEE from the activity record (AR) and triaxial accelerometer (ACC). RESULTS: TEEDLW (3172 ± 415 kcal/day) was not significantly different from EERNIHN (p = 0.076) or EERJISS (p = 0.967). In addition, there were no significant differences between TEEDLW and TEEAR (p = 0.218). However, two accelerometer-derived equations used to evaluate TEE were found to have underestimated (2783 ± 377 kcal/day, p < 0.001) and overestimated (3405 ± 369 kcal/day, p = 0.009) the TEE. CONCLUSION: Our results suggest that EERNIHN and EERJISS may be useful in evaluating the EER of collegiate male sprinters on a group basis, and AR may be more accurate than ACC in evaluating the TEE. These results may be helpful when considering nutritional support for male collegiate sprinters.


Asunto(s)
Acelerometría , Composición Corporal , Metabolismo Energético , Humanos , Masculino , Adulto Joven , Acelerometría/métodos , Necesidades Nutricionales , Carrera/fisiología , Agua , Atletas , Ingestión de Energía , Japón
9.
J Org Chem ; 89(9): 6377-6388, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38634731

RESUMEN

The stereoselective 5-endo-trig oxygenative cyclization of α,ß-unsaturated oximes was achieved using molecular oxygen (O2) and a manganese catalyst. Several 4-hydroxy-4,5-dihydroisoxazoles were obtained in high yields by directly incorporating O2 from the atmosphere (eliminating the necessity for a pure oxygen environment) and using an unprecedentedly low loading of Mn(acac)3 (as little as 0.020 mol %) without additional additives. Because of its desirable features, such as operational simplicity, inexpensive catalyst, mild reaction conditions (open flask conditions at room temperature), and broad substrate compatibility, this novel reaction provides an attractive synthetic approach to producing 4-hydroxy-4,5-dihydroisoxazoles.

10.
J Laparoendosc Adv Surg Tech A ; 34(5): 393-400, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38593412

RESUMEN

Introduction: The use of robotic platform for gastrectomy for gastric cancer is rapidly increasing. This study aimed to describe the perioperative outcomes of 12 patients who underwent robotic gastrectomy for gastric cancer using the hinotori™ surgical robot system (hinotori), a novel robot-assisted surgical platform, and compare the outcomes with the existing system, the da Vinci® Surgical System (DVSS). Methods: This study included 12 consecutive patients with gastric cancer who underwent robotic gastrectomy for gastric cancer using the hinotori between March 2023 and September 2023 at our institution. The comprehensive perioperative outcomes of these patients were retrospectively analyzed and compared to 11 patients who underwent robotic gastrectomy using the DVSS during the same period. Results: The median age and body mass index were 71 years (range: 56-86) and 22.7 kg/m2 (range: 16.1-26.7). Distal and total gastrectomy were performed in 8 and 4 patients, respectively. The median console time and operation times were 187 (range: 112-270) and 252 minutes (range: 173-339), respectively. The median blood loss was 3 mL (range: 2-5). No intra- or postoperative complications were observed. There were no significant differences in perioperative outcomes between the hinotori and the DVSS. Conclusions: Robotic gastrectomy for gastric cancer using the hinotori is a feasible procedure and achieved perioperative outcomes similar to that using the DVSS. Clinical Trial Registration number: 114167-1.


Asunto(s)
Gastrectomía , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Gastrectomía/métodos , Gastrectomía/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/instrumentación , Persona de Mediana Edad , Femenino , Masculino , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Tempo Operativo , Resultado del Tratamiento
11.
J Neurosurg Case Lessons ; 7(11)2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38467048

RESUMEN

BACKGROUND: The treatment strategy for hemorrhagic moyamoya disease (MMD) due to a ruptured aneurysm at the distal portion of the anterior choroidal artery remains controversial. The authors successfully treated the ruptured aneurysm with neuroendoscopic hematoma evacuation, followed by endovascular coil embolization. OBSERVATIONS: The authors encountered two patients with massive hemorrhagic MMD whose MMD had already been diagnosed and who had a periventricular anastomosis due to a ruptured aneurysm of the distal portion of the anterior choroidal artery involving the periventricular anastomosis. In both cases, neuroendoscopic hematoma evacuation was performed for hemorrhagic MMD in the acute phase, followed by endovascular coil embolization of the ruptured aneurysm in the chronic phase. In both endovascular treatments, the patient's condition was stabilized by hematoma evacuation, allowing a detailed preoperative evaluation of the anatomical findings of the vessel and functional findings of intraoperative neurophysiological monitoring using continuous monitoring of motor evoked potentials to preserve motor function. LESSONS: Combination therapy can be useful for hemorrhagic MMD in patients with diagnosed MMD with a periventricular anastomosis. Additionally, a preoperative understanding of the vascular construction and intraoperative neurophysiological monitoring will aid in the successful coil embolization of aneurysms at the distal portion of the anterior choroidal artery with hemorrhagic MMD.

12.
Sci Rep ; 14(1): 6394, 2024 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493174

RESUMEN

The underwater environment is filled with various sounds, with its soundscape composed of biological, geographical, and anthropological sounds. Our work focused on developing a novel method to observe and classify these sounds, enriching our understanding of the underwater ecosystem. We constructed a biologging system allowing near-real-time observation of underwater soundscapes. Utilizing deep-learning-based edge processing, this system classifies the sources of sounds, and upon the tagged animal surfacing, it transmits positional data, results of sound source classification, and sensor readings such as depth and temperature. To test the system, we attached the logger to sea turtles (Chelonia mydas) and collected data through a cellular network. The data provided information on the location-specific sounds detected by the sea turtles, suggesting the possibility to infer the distribution of specific species of organisms over time. The data showed that not only biological sounds but also geographical and anthropological sounds can be classified, highlighting the potential for conducting multi-point and long-term observations to monitor the distribution patterns of various sound sources. This system, which can be considered an autonomous mobile platform for oceanographic observations, including soundscapes, has significant potential to enhance our understanding of acoustic diversity.


Asunto(s)
Ecosistema , Tortugas , Animales , Sonido , Acústica , Recolección de Datos
13.
Oncol Lett ; 27(4): 147, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38385106

RESUMEN

Reflux of gastroduodenal contents into the esophagus leads to the development of esophagitis and inflammation-associated pathologies, such as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The role of the lipoxygenase (LOX) pathway in carcinogenesis has been recently reported; however, its involvement in esophageal carcinogenesis remains unclear. To address this, the present study investigated the potential of pranlukast, a cysteinyl leukotriene receptor-1 antagonist, to suppress the progression of BE and EAC in a rat duodenogastroesophageal reflux (DGER) model. Male Wistar rats that underwent DGER were divided into two groups. One group was fed commercial chow (control group), and the other was fed experimental chow containing pranlukast (pranlukast group). The rats were sacrificed at 10, 20, 30 and 40 weeks after surgery, and their esophagi were examined. Expression levels of 5-LOX, CD68, IL-8, VEGF and Ki-67 were investigated using immunohistochemistry, and apoptosis was analyzed using the TUNEL method. In the pranlukast group, esophagitis was milder, and the incidence of BE and EAC was significantly lower (P<0.05) compared with that in the control group at 40 weeks after surgery. The number of cells positive for IL-8 and VEGF were significantly lower in the pranlukast group compared with the control group. Proliferative activity was also lower in the pranlukast group compared with the control group (P<0.05). Pranlukast treatment increased apoptosis (P<0.05). Overall, Pranlukast suppressed esophageal carcinogenesis in a rat DGER model, decreasing inflammatory cytokines such as IL-8 and VEGF.

14.
Drug Discov Ther ; 18(1): 54-59, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38417897

RESUMEN

The shift towards community-based care in Japan has led to increased medication assistance for older people by non-medical care staff. These staff members help take pre-packaged medications, apply patches, and administer eye drops. This study assessed the risks associated with such assistance by reviewing medication-related incidents across 106 residential care facilities between April 1, 2015, and March 31, 2016. An analysis of incident reports showed that all incidents were minor, with no serious outcomes. The incidents were categorized into four types: dropped drugs, misdelivery/misuse of medicines, forgetting to take medicines, and loss of medicines, with dropped drugs being the most frequent. Most incidents occurred in the morning and primarily involved residents with intermediate nursing care needs. These findings indicate a low risk of serious incidents because of medication assistance from non-medical staff. However, the frequency and nature of the incidents were influenced by the timing of medication administration and the care needs of the residents. These insights highlight the need for customized approaches to medication assistance, considering the residents' care levels and potentially optimizing medication administration times to improve safety in residential care settings.


Asunto(s)
Gestión de Riesgos , Humanos , Anciano , Japón
15.
Sci Rep ; 14(1): 3740, 2024 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355873

RESUMEN

Drosophila melanogaster has a pair of male-specific muscles called the muscle of Lawrence (MOL) in abdominal segment 5 (A5) of adult flies. The MOL is produced only when its innervating motoneuron expresses FruitlessM (FruM) neural masculinizing proteins. We show that MOL induction is hampered by: (1) silencing electrical activities in the motoneuron, (2) blocking vesicular release from the motoneuron, and (3) knocking down Activin ß (Actß) in the motoneuron or knocking down Actß signaling pathway components in the myoblasts. Our timelapse live imaging of the developing neuromuscular system reveals that, upon contact with the presumptive MOL, the motoneuronal axon retracts concomitant with the progression of MOL degeneration resulting from neural silencing. We conclude that MOL formation depends on the bidirectional trophic interactions between pre- and postsynaptic cells, with motoneuron-derived Actß playing an inducing role in MOL formation.


Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Masculino , Drosophila melanogaster , Activinas , Proteínas de Drosophila/genética , Músculos Abdominales , Axones
16.
Spine (Phila Pa 1976) ; 49(3): 188-196, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37942814

RESUMEN

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Using a network meta-analysis (NMA), this study aimed to compare the risks of C5 palsy after three different procedures of anterior cervical decompression. SUMMARY OF BACKGROUND DATA: C5 palsy is a well-known complication affecting the quality of life after anterior procedures. Due to the limited evidence on the various procedures available, we evaluate the basis for selection to prevent palsy and achieve maximal decompression in cases spanning 3-6 levels. MATERIALS AND METHODS: We conducted a comprehensive search for C5 palsy and complications after 3representative procedures, including anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and their combination (hybrid), involving 3 to 6 intervertebral levels. The incidence of C5 palsy was compared using a NMA. RESULTS: We identified 1655 patients in 11 studies who met inclusion criteria. Sixty-nine patients (4.2%) developed delayed C5 palsies. The incidences among ACDF, ACCF, and hybrid cases were 2.3% (16/684, 95% CI: 1.4% to 3.8%), 6.4% (39/613, 95% CI: 4.7% to 8.6%), and 3.9% (14/358, 95% CI: 2.3% to 6.5%), respectively ( P < 0.01). A NMA was performed for 15 pairwise comparisons across the 3 procedure arms: ACDF versus hybrid, 7/232 (3.0%) versus 11/234 (4.7%); hybrid versus ACCF, 14/301 (4.3%) versus 18/224 (8.0%); ACCF versus ACDF, 38/523 (7.8%) versus 16/619 (2.6%). Compared with ACDF, the risk of C5 palsy was significantly higher in ACCF (odds ratio: 2.72, 95% CI: 1.47 to 5.01), whereas ACDF versus hybrid did not significantly differ in risk (odds ratio: 1.56, 95% CI: 0.68 to 3.60). CONCLUSION: We determined that ACCF was associated with a higher risk of postoperative C5 palsy than ACDF in cases spanning 3 to 6 intervertebral levels. If practicable, ACDF surgery may be an appropriate choice for cases requiring anterior decompression of 3 to 6 levels. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Fusión Vertebral , Espondilosis , Humanos , Metaanálisis en Red , Calidad de Vida , Fusión Vertebral/métodos , Espondilosis/cirugía , Vértebras Cervicales/cirugía , Discectomía/efectos adversos , Descompresión Quirúrgica/efectos adversos , Parálisis/etiología , Resultado del Tratamiento , Estudios Retrospectivos
17.
iScience ; 26(12): 108471, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38077151

RESUMEN

KcsA is a potassium channel with a plethora of structural and functional information, but its activity in the KcsA-producing actinomycete membranes remains elusive. To determine lipid species involved in channel-modulation, a surface plasmon resonance (SPR)-based methodology, characterized by immobilization of membrane proteins under a membrane environment, was applied. Dianionic cardiolipin (CL) showed extremely higher affinity for KcsA than monoanionic lipids. The SPR experiments further demonstrated that CL bound not only to the N-terminal M0 helix, a lipid-sensor domain, but to the M0 helix-deleted mutant. In contrast, monoanionic lipids interacted primarily with the M0 helix. This indicates the presence of an alternative CL-binding site, plausibly in the transmembrane domain. Single-channel recordings demonstrated that CL enhanced channel opening in an M0-independent manner. Taken together, the action of monoanionic lipids is exclusively mediated by the M0 helix, while CL binds both the M0 helix and its specific site, further enhancing the channel activity.

18.
Insects ; 14(12)2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38132614

RESUMEN

Resilin is an elastic protein that is vital to insects' vigorous movement. Canonical resilin proteins possess the R&R Consensus, a chitin-binding domain conserved in a family of cuticular proteins, and highly repetitive sequences conferring elastic properties. In the malaria vector mosquito, Anopheles gambiae, however, a cuticular protein has been found that has an R&R Consensus resembling that of resilin but lacks the repetitive sequences (here, we call it resilin-related or resilin-r). The relationship between resilin-r and resilin was unclear. It was also unknown whether resilin-r is conserved in mosquitoes. In this paper, phylogenetic and structural analyses were performed to reveal the relationship of resilin homologous proteins from holometabolous insects. Their chitin-binding abilities were also assessed. A resilin-r was found in each mosquito species, and these proteins constitute a clade with resilin from other insects based on the R&R Consensus sequences, indicating an evolutionary relationship between resilin-r and resilin. The resilin-r showed chitin-binding activity as same as resilin, but had distinct structural features from resilin, suggesting that it plays specialized roles in the mosquito cuticle. Another resilin-like protein was found to exist in each holometabolous insect that possesses resilin-like repetitive sequences but lacks the R&R Consensus. These results suggest that similar evolutionary events occurred to create resilin-r and resilin-like proteins.

19.
Inflamm Intest Dis ; 8(4): 133-142, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38115911

RESUMEN

Introduction: Leucine-rich alpha-2-glycoprotein (LRG) is a potential biomarker for disease activity and reflects mucosal healing in patients with ulcerative colitis (UC). However, only a few studies have described a detailed sensitivity analysis of LRG in predicting mucosal healing in patients. This study aimed to evaluate the association between LRG and the endoscopic activity of UC and its predictability for mucosal healing and explore the utility and clinical application of LRG. Methods: The diagnostic accuracy of biomarkers, including LRG, in predicting the endoscopic activity of UC was evaluated. All consecutive patients who underwent total colonoscopy between April 2021 and September 2022 were included. The Mayo endoscopic subscore (MES) was used for assessing endoscopic activity. Furthermore, endoscopic remission was defined as an MES of ≤1. Clinical activity was evaluated based on stool frequency and bloody stool. Receiver operating characteristic curve analysis and binary logistic regression were performed to assess the diagnostic accuracy of the biomarkers. We evaluated LRG trends and treatment response in patients with MES ≥2 who underwent induction therapy. Results: This study comprised 214 patients. The proportions of endoscopically and clinically active patients were 33.6% and 49.1%, respectively. LRG had an area under the curve (AUC) of 0.856, with a higher diagnostic accuracy than other biomarkers, such as C-reactive protein, leukocyte, neutrophil, platelet, and albumin. The cutoff value for LRG was 15.6 µg/mL (sensitivity, 72.2%; specificity, 86.6%). Using the MES, patients with higher scores had higher LRG levels than those with lower scores. The cutoff value, AUC, sensitivity, and specificity varied with a higher AUC for left-sided colitis and pancolitis than for proctitis. Logistic regression analysis showed that LRG was an independent predictor of endoscopic remission using multivariate analysis, even with the factor of clinical activity. The change ratio of LRG pre- and post-treatment was statistically significant in the higher LRG group. Conclusion: LRG reflected endoscopic activity independently, regardless of clinical symptoms. An LRG below the cutoff value could indicate a significantly low probability of endoscopic activity in asymptomatic patients, and follow-up endoscopy (not for cancer screening) may be unnecessary. Furthermore, a higher LRG level might be more useful as an indicator of treatment efficacy.

20.
Artículo en Inglés | MEDLINE | ID: mdl-37999771

RESUMEN

PURPOSE: In Japan, the vehicle used in pre-hospital trauma care systems with physician-staffed ground emergency medical services (GEMS) is referred to as a "doctor car". Doctor cars are highly mobile physician-staffed GEMS that can provide complex pre-hospital trauma management using various treatment strategies. The number of doctor car operations for patients with severe trauma has increased. Considering facility factors, the association between doctor cars and patient outcomes remains unclear. Therefore, this study aimed to examine the relationship between doctor cars for patients with severe trauma and survival outcomes in Japan. METHODS: A nationwide retrospective cohort study was conducted to compare the impact of the doctor car group with the non-physician-staffed GEMS group on in-hospital survival in adult patients with severe trauma. The data were analyzed using multivariable logistic regression models with generalized estimating equations. RESULTS: This study included 372,365 patients registered in the Japan Trauma Data Bank between April 2009 and March 2019. Of the 49,144 eligible patients, 2361 and 46,783 were classified into the doctor car and non-physician staffed GEMS groups, respectively. The adjusted odds ratio (OR) for survival was significantly higher in the doctor car group than in the non-physician staffed GEMS group (adjusted OR = 1.228 [95% confidence interval 1.065-1.415]). CONCLUSION: Using nationwide data, this novel study suggests that doctor cars improve the in-hospital survival rate of patients with severe trauma in Japan. Therefore, doctor cars could be an option for trauma strategies.

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