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Background: The role of non-linguistic factors, such as executive functions, in the reading comprehension process has been analyzed. The present research sought to investigate the relationship between executive functions and reading comprehension. Methods: In an exploratory cross-sectional study, a group of 89 fourth-grade students were evaluated, considering a balanced number of children with and without reading comprehension difficulties. Results: The results indicate that students with reading comprehension difficulties present a lowered profile with respect to both executive functions and reading variables. The path analysis indicates the presence of differences in the variables that explain reading comprehension for both groups. While in the case of students without reading comprehension difficulties, working memory has both a direct and an indirect effect, i.e., through vocabulary, on reading comprehension; in the case of children with reading comprehension difficulties, only cognitive flexibility has a direct impact. In both cases, inhibition has an indirect impact through vocabulary. Conclusions: We reflect on the differentiated role of executive functions according to the level of development of reading skills, highlighting the possibility that some skills may act in a compensatory manner in the presence of general difficulties. The role of vocabulary in the relationship between executive skills and reading is highlighted. [ABSTRACT FROM AUTHOR]

Introduction: Severe depression is a prevalent psychiatric illness in children and adolescents associated with high levels of morbidity, disability, and a high risk of suicidal behavior. Cognitive factors associated with depression severity in juveniles have been poorly reported. Methods: We investigated the relationship between depression severity and intelligence quotient (IQ)with its subscales in 65 juveniles (aged 10–17 years) with a current major depressive episode evaluated at the Mood Disorder Program of Bambino Gesù Children's Hospital in Rome. Pearson's correlation analyses were followed by a Benjamini–Hochberg correction and linear multivariable regression model. Results: Depression severity measured with the total score of the Children's Depression Rating Scale-Revised (CDRS-R) was positively associated with the Verbal Comprehension Index (VCI; Pearson's r = 0.309 [0.042−0.534]; p = 0.024). The CDRS-R subscales positively associated with VCI by Pearson's correlation were depressed feelings, suicidal ideation, excessive weeping, and reduced facial expressions. Suicidal ideation was the only factor independently and significantly associated with higher VCI in the multivariable linear regression model. Discussion: Suicidal ideation was significantly and independently associated with higher verbal comprehension, indicating that depressed juveniles with better verbal ability may be at a greater risk of showing suicidal ideation. [ABSTRACT FROM AUTHOR]

We start from the premise that reading is a permanent process of interaction between reader and text, in which the subjects rely both on certain purposes that guide the reading and on their previous knowledge and experiences, in order to produce meanings and effectively understand the texts. In this perspective, the research aims to identify how literary reading, from the proposal of strategies, can contribute to the process of reading comprehension of children in the literacy phase. For this, the proposed investigation is configured in a participatory research, of qualitative approach and of descriptive character, taking as technical and investigative procedure the systematic observation, from the application of reading activities, during the school year of 2022, in a class of the 1st year of elementary school, of a school of the municipal network, located in Campo das Vertentes, Minas Gerais. As a theoretical basis, we highlight the studies of Solé (1998) regarding reading strategies and Girotto and Souza (2010) regarding strategies specifically directed to literary reading. The results of the research reveal the importance of planning pedagogical actions that favor literary reading strategies in an educational context, as such stimuli contribute to the process of reading comprehension by children, significantly favoring the formation of autonomous, critical and reflective readers. [ABSTRACT FROM AUTHOR]

The objective of this research is to develop reading comprehension strategies in a group of 3 fifth grade school-aged children with difficulties in reading comprehension (impairment of the understanding of sentences with a complex logicalgrammatical structure due to the constant loss of the objective of the activity) and low cognitive motivation. A pre-test and post-test evaluation was carried out after the application of the intervention. The intervention program was based on the formation of the zone of proximal development, the guiding basis of action, the formation of mental actions in stages and the gradual formation of brain mechanisms identified with weaknesses through shared reading activities in which used and analyzed language. The results show that the activity regulation strategies used by the children for reading comprehension after the intervention were: they identify the objective in the text considering its structure, they use graphic representations to organize and classify the information, they reread some sections, take notes, underline important words and ideas. Regarding the strategy that involves cognitive motivation after the intervention, the dialogic conversation with other readers, establishing relationships between the texts, stood out. It is concluded that both the activity regulation strategies and the strategies that involve cognitive motivation favor the interaction between the reader and the text and the relationship between the reader and other readers due to the emotional content that the texts generate in the dialogic interaction. [ABSTRACT FROM AUTHOR]

Digital picture-book (DPB) with animated elements can enhance children's engagement, but irrelevant animations may interfere with their comprehension. To determine the effect of the relevance of animated elements on preschoolers' comprehension, an experimental study was conducted. Thirty-three preschoolers between the aged 4-5 years engaged with DPB in three conditions: high- and low-relevant animations and a static control while listening to the story; their eye movements were recorded simultaneously. The study found that preschoolers had lower comprehension when exposed to low-relevant animation, but had comparable scores to the static condition with high-relevant animation. The results of eye-movement analysis showed that children who focused less on high-relevant or more on low-relevant elements had poorer comprehension. Those exposed to low-relevant animations looked less at high-relevant elements and more at low-relevant elements than those in the static and high-relevant conditions. These results suggested that low-relevant animations in DPB interfered with children's comprehension by directing their visual attention away from crucial, high-relevant elements and more to less relevant elements. Therefore, designers creating DPBs, as well as parents and caregivers selecting DPBs for children, should consider the importance of the relevance of animated elements. And the corresponding mechanism of animation effect in DPB comprehension was discussed. [ABSTRACT FROM AUTHOR]

Introduction: The acquisition of reading skills is a crucial milestone in early education, with formal instruction and practice playing pivotal roles. The outbreak of COVID-19 led to widespread school closures and a shift to remote learning. Methods: This study aimed to investigate the effects of school closures on reading acquisition and fluency among a large sample of second-grade children, considering socioeconomic status (SES) and gender differences. In 2019, a cohort of 2228 second-grade students from 34 schools was assessed for word reading fluency and comprehension. In 2020, during the pandemic, 765 students from a subsample of 20 original schools were re-evaluated using the same measures. The study also collected school-related data. Results: The findings from the entire sample indicated no significant differences in fluency and comprehension scores between children in the second grade in 2019 and 2020. However, a significant interaction emerged when analyzing low SES versus high SES children. Children from low SES backgrounds exhibited notably lower reading scores after a year of remote learning due to the COVID-19 outbreak. Moreover, the disparity in reading scores between low SES and high SES children nearly doubled in 2020. Gender differences were also detected. Discussion: These results underscore the impact of remote learning during the COVID-19 crisis on exacerbating gaps in reading fluency and comprehension between children from high and low SES backgrounds. The implications of these findings highlight the critical role of in-person schooling and targeted support for disadvantaged students, especially during pivotal stages of reading development. [ABSTRACT FROM AUTHOR]

Benefit recipients, particularly those with developmental disabilities, require ongoing rehabilitation treatments. Sustainable rehabilitation services are not feasible for a number of reasons, particularly in low- and middleincome nations. The best approach for long-term rehabilitation treatments for kids with developmental problems is parent-mediated intervention. This narrative review attempts to give readers a general understanding of parent-mediated intervention, including its advantages, drawbacks, and determining factors. Google Scholar and PubMed computer searches were used to compile the papers. This study's findings indicate that the main factors supporting parent-mediated intervention are financial hardship, difficulty accessing rehabilitation facilities, and lack of availability of rehabilitation professionals. It gives kids a better learning environment and parent-child connection so they can communicate and learn more effectively. Additionally, it aids in the parent's comprehension of their child, enabling them to train them more effectively while lowering their stress levels and other discomforts. At the same time, Parents want appropriate direction and perhaps in-depth instruction from their rehabilitation specialists. To learn about the requirements, rewards, and paperwork, parents must receive training. [ABSTRACT FROM AUTHOR]

"Are you LISTENING?" may be one of the most frequent questions preschoolers hear from their parents and teachers, but can children be taught to listen carefully—and thus better comprehend language—and if so, what changes occur in their brains? Twenty-seven four- and five-year-old children were taught a language simulation strategy to use while listening to stories: first, they practiced moving graphics on an iPad to correspond to the story actions, and then they practiced imagining the movements. Compared to a control condition, children in the intervention answered comprehension questions more accurately when imagining moving the graphics and on a measure of transfer using a new story without any instruction and with only immovable graphics. Importantly, for children in the intervention, the change in comprehension from the first to the sixth day was strongly correlated with changes in EEG mu and alpha desynchronization, suggesting changes in motor and visual processing following the intervention. Thus, the data are consistent with our hypothesis that a language simulation listening comprehension intervention can improve children's listening comprehension by teaching children to align visual and motor processing with language comprehension. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to develop and validate a modified version of the Speech in Noise Sentence Test in Kannada, which would be appropriate for testing the speech comprehension ability of children aged 8-12 years. Subjects and Methods: A total of 120 sentences were chosen from 200 familiar sentences and split into four lists. Continuous discourse was used as a competition or distractor. Using MATLAB, the target stimulus was presented at 0-degree azimuth while the distractor's location varied (+90° and -90° azimuth). The test was programmed to dynamically adjust the signal-to-noise ratio (SNR) based on participants' responses. After initial validation, a pilot study was conducted with 60 typically hearing children aged 8 to 12 years. Results: The SNR50 scores significantly improved when the distractor and target sentences were spatially separated across all groups. Age had a significant influence on the spatial separation scores. The test-retest reliability was excellent. Conclusions: The developed stimuli effectively measured spatial separation, and the normative and psychometric analyses demonstrated reliable outcomes. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Theoretical Educational Science / Kuramsal Eğitimbilim Dergisi is the property of Afyon Kocatepe University, Faculty of Education and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The current study investigated the effects of inference instruction on text-based inferences by third graders who are below average in reading comprehension but average in reading fluency and cognitive abilities. Textbased inferences occur when the preceding text has an identifiable causal antecedent. Participants were randomly assigned and attended twelve 30- minute sessions of the inferences training intervention. We have included strategies for integrating information from the text to improve reading comprehension skills. We provide an overview of how specific text-based instruction influences reading comprehension processes and outcomes and can lead to increased reading comprehension. The comparison of pretest and posttest results in the experimental group showed a significant gain in the following variables: generating inferences and providing arguments for using rules and constraints. Finally, we discuss how consideration of these potential sources of instruction has practical implications for designing and selecting instructional materials. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Elementary Education / Revija za Elementarno Izobraževanje is the property of University of Maribor, Faculty of Education and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this study, we investigated the comprehension of metonymy with children aged 3 to 8 years old, by replicating the method of the Köder and Falkum (2020) study, from the Cognitive Linguistics perspective. In the test, 133 participants, children and adults, were exposed to a visual stimulus, which consists of a set of images, and an auditory stimulus, which consists of a literal or metonymic vignette. The results obtained in this work partially corroborate the result of the original study (Köder; Falkum, 2020), in which there was a significant difference in the comprehension of metonymy in the different age groups studied. Here, the level of metonymic comprehension of this task did not increase at 6 years of age, as in the replicated study, and some hypotheses for this change are formulated. Also, the 8-year-old children's level of comprehension turned out not to be similar to the comprehension of the adult control group. In addition, significant differences were also found between the literal and metonymic conditions, regarding the levels of comprehension. From this general result, issues that may have led to this result are discussed, involving both age and linguistic cultural influences. [ABSTRACT FROM AUTHOR]

Copyright of Revista Soletras is the property of Editora da Universidade do Estado do Rio de Janeiro (EdUERJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Reading comprehension is one of the most important skills learned in school and it has an important contribution to the academic success of children with Autism Spectrum Disorder (ASD). Though previous studies have investigated reading comprehension difficulties in ASD and highlighted factors that contribute to these difficulties, this evidence has mainly stemmed from children with ASD and intact cognitive skills. Also, much emphasis has been placed on the relation between reading comprehension and word recognition skills, while the role of other skills, including fluency and morphosyntax, remains underexplored. This study addresses these gaps by investigating reading comprehension in two groups of school-aged children with ASD, one with intact and one with low cognitive abilities, also exploring the roles of word decoding, fluency and morphosyntax in each group’s reading comprehension performance. Methods: The study recruited 16 children with ASD and low cognitive abilities, and 22 age-matched children with ASD and intact cognitive skills. The children were assessed on four reading subdomains, namely, decoding, fluency, morphosyntax, and reading comprehension. Results: The children with ASD and low cognitive abilities scored significantly lower than their peers with intact cognitive abilities in all reading subdomains, except for decoding, verb production and compound word formation. Regression analyses showed that reading comprehension in the group with ASD and intact cognitive abilities was independently driven by their decoding and fluency skills, and to a lesser extent, by morphosyntax. On the other hand, the children with ASD and low cognitive abilities mainly drew on their decoding, and to a lesser extent, their morphosyntactic skills to perform in reading comprehension. Discussion: The results suggest that reading comprehension was more strongly affected in the children with ASD and low cognitive abilities as compared to those with intact cognitive skills. About half of the children with ASD and intact cognitive skills also exhibited mild-to-moderate reading comprehension difficulties, further implying that ASD may influence reading comprehension regardless of cognitive functioning. Finally, strengths in decoding seemed to predominantly drive cognitively-impaired children’s reading performance, while the group with ASD and intact cognitive skills mainly recruited fluency and metalinguistic lexical skills to cope with reading comprehension demands, further suggesting that metalinguistic awareness may be a viable way to enhance reading comprehension in ASD. [ABSTRACT FROM AUTHOR]

Early endosomes (EEs) are crucial in cargo sorting within vesicular trafficking. While cargoes destined for degradation are retained in EEs and eventually transported to lysosomes, recycled cargoes for the plasma membrane (PM) or the Golgi undergo segregation into specialized membrane structures known as EE buds during cargo sorting. Despite this significance, the molecular basis of the membrane expansion during EE bud formation has been poorly understood. In this study, we identify a protein complex comprising SHIP164, an ATPase RhoBTB3, and a retromer subunit Vps26B, which promotes the formation of EE buds at Golgi–EE contacts. Our findings reveal that Vps26B acts as a novel Rab14 effector, and Rab14 activity regulates the association of SHIP164 with EEs. Depletion of SHIP164 leads to enlarged Rab14+ EEs without buds, a phenotype rescued by wild-type SHIP164 but not the lipid transfer-defective mutants. Suppression of RhoBTB3 or Vps26B mirrors the effects of SHIP164 depletion. Together, we propose a lipid transport-dependent pathway mediated by the RhoBTB3–SHIP164–Vps26B complex at Golgi–EE contacts, which is essential for EE budding. [ABSTRACT FROM AUTHOR]

Focus structures, a complex aspect of information structure in language, have garnered significant attention in psycholinguistics. The question of whether Chinese preschoolers aged 4–6 years possess the ability to process focus structures in oral communication, and how cognitive factors influence this ability, remains a research focal point. To address this, we recruited 100 Chinese preschoolers aged 4–6 years as participants in our study. This study manipulated the positions of focus particles in sentences to investigate the impact of phonological awareness on young children's comprehension of focus structures. Additionally, we examined the mediating roles of cognitive flexibility and inhibitory control. Our findings indicate the following: (1) phonological awareness positively predicted the accuracy of focus structural processing; (2) inhibitory control did not significantly predict the accuracy of focus structural processing; and (3) cognitive flexibility partially mediated the relationship between phonological awareness and focus structural comprehension. These results confirmed the predictive effect of cognitive flexibility on children's comprehension of focus structures. Moreover, they demonstrate that young children's phonological awareness can predict their focus structure comprehension ability through the mediating role of cognitive flexibility. This suggests that children's cognitive flexibility can aid in understanding sentences with focus structures. [ABSTRACT FROM AUTHOR]

While 3D tumor models have greatly evolved over the past years, there is still a strong requirement for more biosimilar models which are capable of recapitulating cellular crosstalk within the tumor microenvironment while equally displaying representative levels of tumor aggressiveness and invasion. Herein, we disclose an assembloid melanoma model based on the fusion of individual stromal multicellular spheroids (MCSs). In contrast to more traditional tumor models, we show that it is possible to develop self-organizing, heterotypic melanoma models where tumor cells present stem-cell like features like up-regulated pluripotency master regulators SOX2, POU5F1 and NANOG. Additionally, these assembloids display high levels of invasiveness while embedded in 3D matrices as evidenced by stromal cell promotion of melanoma cell invasion via metalloproteinase production. Furthermore, sensitivity to anticancer drug doxorubicin was demonstrated for the melanoma assembloid model. These findings suggest that melanoma assembloids may play a significant role in the field of 3D cancer models as they more closely mimic the tumor microenvironment when compared to more traditional MCSs, opening the doors to a better understanding of the role of tumor microenvironment in supporting tumor progression. The development of complex 3D tumor models that better recapitulate the tumor microenvironment is crucial for both an improved comprehension of intercellular crosstalk and for more efficient drug screening. We have herein developed a self-organizing heterotypic assembloid-based melanoma model capable of closely mimicking the tumor microenvironment. Key features recapitulated were the preservation of cancer cell stemness, sensitivity to anti-cancer agents and tumor cell invasion promoted by stromal cells. The approach of pre-establishing distinct stromal domains for subsequent combination into more complex tumor constructs provides a route for developing superior tumor models with a higher degree of similarity to native cancer tissues. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of REICE. Ibero-American Journal on Quality, Effectiveness & Change in Education / REICE. Revista Iberoamericana Sobre Calidad, Eficacia y Cambio en Educación is the property of Red Iberoamericana de Investigacion sobre Cambio y Eficacia en Educacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The purpose of this study was to apply and analyze the impact of the semantic feature analysis (SFA) strategy on vocabulary development and comprehension of texts and theoretical concepts in Portuguese school-age students with and without special educational needs (SEN) attending inclusive schools. Method: The research design was quasi-experimental. The SFA was administered in ten sessions of approximately 60 min each. The sample was a convenience sample and consisted of selecting three classes in each school: (i) in the first cycle of basic education, 65 students were divided into a control group, an experimental group and a structured teaching group; (ii) in the second cycle of basic education, 55 students were divided into an experimental group, an online virtual school and a control group. Results: (1) The SFA strategy is motivating, appealing, inexpensive, flexible and easy to implement; (2) learning the SFA strategy is easy and can be successfully taught in any classroom; (3) the performance of the students assigned to the experimental groups was significantly higher in both cycles compared to all the other groups; (4) the effect sizes were 0.87 in the first cycle and 0.88 in the second cycle. Conclusion: The SFA strategy effectively promotes the development of vocabulary, concept knowledge and text comprehension in school-age children, being more effective than regular teaching. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity and impulsivity that may begin in early childhood and continue into adolescence and adulthood and are incompatible with the developmental level of the individual. Most children with ADHD are at risk of facing significant academic problems throughout their educational life. In recent studies aiming to reveal the causes of academic problems experienced by children with ADHD, academic problems have been associated with the difficulties in reading and listening comprehension skills of children with ADHD. The relatively common prevalence of ADHD, the extent of academic problems experienced by children with ADHD, and the lack of clarity about reading difficulties require further examination of the relationship between ADHD and reading and listening comprehension skills, which are often based on the same language and cognitive skills. Listening comprehension, which is defined as the ability to understand, interpret, organize, and evaluate the ideas and thoughts in a speech heard or a text read aloud, is one of the most important early literacy skills necessary for the ultimate goal of reading, which is reading comprehension. In this review study, listening comprehension skills of children with ADHD were discussed together with the literature. [ABSTRACT FROM AUTHOR]

Mapping genetic variations to phenotypic variations poses a significant challenge, as mutations often combine unexpectedly, diverging from assumed additive effects even in the same environment. These interactions are known as epistasis or genetic interactions. Sign epistasis, as a specific type of epistasis, involves a complete reversal of mutation effects within altered genetic backgrounds, presenting a substantial hurdle to phenotype prediction. Despite its importance, there is a limited systematic overview of the mechanistic causes of sign epistasis. This review explores the mechanistic causes, highlighting its occurrence in signalling cascades, peaked fitness landscapes, and physical interactions. Moving beyond theoretical discussions, we delve into the practical applications of sign epistasis in agriculture, evolution, and antibiotic resistance. In conclusion, this review aims to enhance the comprehension of sign epistasis and molecular dynamics, anticipating future endeavours in systematic biology engineering that leverage the knowledge of sign epistasis. [ABSTRACT FROM AUTHOR]

Advances in the field of genomics and transcriptomics have enabled researchers to identify gene signatures related to development and treatment of Small Cell Lung Cancer. In most cases, complex gene expression patterns are identified, comprising of genes with differential behavior. Most tools use single-genes as predictors of drug response, with only limited options for multi-gene use. Here we examine the potential of predicting drug response using these complex gene expression signatures by employing clustering and signal enrichment in Small Cell Lung Cancer. Our results demonstrate clustering genes from complex expression patterns helps identify differential activity of gene groups with alternate function which can then be used to predict drug response. • Clustering genes in expression signatures before enrichment analysis helps find key groups • Most small cell lung cancer cell lines are enriched for epithelial genes • A subset of inflamed signature genes used to predict immunotherapy response are not expressed in cell lines [ABSTRACT FROM AUTHOR]

Cytoplasmic dynein 1 (dynein) is the primary minus end-directed motor protein in most eukaryotic cells. Dynein remains in an inactive conformation until the formation of a tripartite complex comprising dynein, its regulator dynactin, and a cargo adaptor. How this process of dynein activation occurs is unclear since it entails the formation of a three-protein complex inside the crowded environs of a cell. Here, we employed live-cell, single-molecule imaging to visualize and track fluorescently tagged dynein. First, we observed that only ~30% of dynein molecules that bound to the microtubule (MT) engaged in minus end-directed movement, and that too for a short duration of ~0.6 s. Next, using high-resolution imaging in live and fixed cells and using correlative light and electron microscopy, we discovered that dynactin and endosomal cargo remained in proximity to each other and to MTs. We then employed two-color imaging to visualize cargo movement effected by single motor binding. Finally, we performed long-term imaging to show that short movements are sufficient to drive cargo to the perinuclear region of the cell. Taken together, we discovered a search mechanism that is facilitated by dynein's frequent MT binding-unbinding kinetics: (i) in a futile event when dynein does not encounter cargo anchored in proximity to the MT, dynein dissociates and diffuses into the cytoplasm, (ii) when dynein encounters cargo and dynactin upon MT binding, it moves cargo in a short run. Several of these short runs are undertaken in succession for long-range directed movement. In conclusion, we demonstrate that dynein activation and cargo capture are coupled in a step that relies on the reduction of dimensionality to enable minus end-directed transport in cellulo and that complex cargo behavior emerges from stochastic motor-cargo interactions. [ABSTRACT FROM AUTHOR]

Simple Summary: Skin cancer represents a prevalent and significant global health concern. Our study focused on comprehending cutaneous squamous cell carcinoma in the Mexican population through the examination of genetic variants of the PTCH1 gene, the assessment of its mRNA's relative expression, and the utilization of bioinformatics tools. Despite the absence of statistically significant associations in the experimental results, integrating bioinformatics was imperative to understand the impact of the analyzed variants on protein function, splicing, expression, and disease-related aspects. This contributes to our overarching comprehension of non-melanoma skin cancer development. Further investigation is crucial to gain a comprehensive understanding of the in vivo role of these genetic variants. Background: Skin cancer is one of the most frequent types of cancer, and cutaneous squamous cell carcinoma (cSCC) constitutes 20% of non-melanoma skin cancer (NMSC) cases. PTCH1, a tumor suppressor gene involved in the Sonic hedgehog signaling pathway, plays a crucial role in neoplastic processes. Methods: An analytical cross-sectional study, encompassing 211 cSCC patients and 290 individuals in a control group (CG), was performed. A subgroup of samples was considered for the relative expression analysis, and the results were obtained using quantitative real-time PCR (qPCR) with TaqMan® probes. The functional, splicing, and disease-causing effects of the proposed variants were explored via bioinformatics. Results: cSCC was predominant in men, especially in sun-exposed areas such as the head and neck. No statistically significant differences were found regarding the rs357564, rs2236405, rs2297086, and rs41313327 variants of PTCH1, or in the risk of cSCC, nor in the mRNA expression between the cSCC group and CG. A functional effect of rs357564 and a disease-causing relation to rs41313327 was identified. Conclusion: The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants. [ABSTRACT FROM AUTHOR]

The lysosome is an acid organelle that contains a variety of hydrolytic enzymes and plays a significant role in intracellular degradation to maintain cellular homeostasis. Genetic variants in lysosome-related genes can lead to severe congenital diseases, such as lysosomal storage diseases. In the present study, we investigated the impact of depleting lysosomal acid lipase A (LIPA), a lysosomal esterase that metabolizes esterified cholesterol or triglyceride, on lysosomal function. Under nutrient-rich conditions, LIPA gene KO (LIPAKO) cells exhibited impaired autophagy, whereas, under starved conditions, they showed normal autophagy. The cause underlying the differential autophagic activity was increased sensitivity of LIPAKO cells to ammonia, which was produced from L-glutamine in the medium. Further investigation revealed that ammonia did not affect upstream signals involved in autophagy induction, autophagosome-lysosome fusion, and hydrolytic enzyme activities in LIPAKO cells. On the other hand, LIPAKO cells showed defective lysosomal acidity upon ammonia loading. Microscopic analyses revealed that lysosomes of LIPAKO cells enlarged, whereas the amount of lysosomal proton pump V-ATPase did not proportionally increase. Since the enlargement of lysosomes in LIPAKO cells was not normalized under starved conditions, this is the primary change that occurred in the LIPAKO cells, and autophagy was affected by impaired lysosomal function under the specific conditions. These findings expand our comprehension of the pathogenesis of Wolman's disease, which is caused by a defect in the LIPA gene, and suggest that conditions, such as hyperlipidemia, may easily disrupt lysosomal functions. [ABSTRACT FROM AUTHOR]

Treatment effectiveness and biosafety are critical for disease therapy. Bio-membrane modification facilitates the homologous targeting of drugs in vivo by exploiting unique antibodies or antigens, thereby enhancing therapeutic efficacy while ensuring biosafety. To further enhance the precision of disease treatment, future research should shift focus from targeted cellular delivery to targeted subcellular delivery. As the cellular powerhouses, mitochondria play an indispensable role in cell growth and regulation and are closely involved in many diseases (e.g. , cancer, cardiovascular, and neurodegenerative diseases). The double-layer membrane wrapped on the surface of mitochondria not only maintains the stability of their internal environment but also plays a crucial role in fundamental biological processes, such as energy generation, metabolite transport, and information communication. A growing body of evidence suggests that various diseases are tightly related to mitochondrial imbalance. Moreover, mitochondria-targeted strategies hold great potential to decrease therapeutic threshold dosage, minimize side effects, and promote the development of precision medicine. Herein, we introduce the structure and function of mitochondrial membranes, summarize and discuss the important role of mitochondrial membrane-targeting materials in disease diagnosis/treatment, and expound the advantages of mitochondrial membrane-assisted drug delivery for disease diagnosis, treatment, and biosafety. This review helps readers understand mitochondria-targeted therapies and promotes the application of mitochondrial membranes in drug delivery. Bio-membrane modification facilitates the homologous targeting of drugs in vivo by exploiting unique antibodies or antigens, thereby enhancing therapeutic efficacy while ensuring biosafety. Compared to cell-targeted treatment, targeting of mitochondria for drug delivery offers higher efficiency and improved biosafety and will promote the development of precision medicine. As a natural material, the mitochondrial membrane exhibits excellent biocompatibility and can serve as a carrier for mitochondria-targeted delivery. This review provides an overview of the structure and function of mitochondrial membranes and explores the potential benefits of utilizing mitochondrial membrane-assisted drug delivery for disease treatment and biosafety. The aim of this review is to enhance readers' comprehension of mitochondrial targeted therapy and to advance the utilization of mitochondrial membrane in drug delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

One important internal factor influencing reading comprehension is a child's executive functioning. The primary objective of this paper is to evaluate the effectiveness of a cognitive stimulation program, ExeFun-READ (a program focusing on executive functioning stimulation via the L1 (Slovak language) curriculum with a specific focus on enhancing reading comprehension). The program is explicitly based on the assumed bi-directional relationship between executive functioning and language abilities related to reading comprehension. The program is domain-specific; the curriculum of L1 (Slovak) is a curricular area in which cognitive mediation occurs. The study will investigate whether the domain-specific ExeFun-READ intervention had a positive effect on children's executive functioning and language subcomponents of reading comprehension. Keeping in mind ecological validity, ExeFun-READ was designed primarily for educational purposes, specifically professional tutoring for low-performing students. The intervention consists of 30 units; each unit lasts for 45–60 min. A stimulation unit approximates a teaching unit rather than a clinical experimental intervention. In total, 151 low-performing students attending grade four from seven elementary schools took part in the project. The study employs a pre-test–training–post-test design with three conditions: experimental, active control, and passive control. In the current study, the intervention led to improved language abilities related to reading comprehension. Significant improvements were found in vocabulary (semantic knowledge), completion of sentences (syntactic knowledge), and classification of terms (verbal fluency and inferencing) in the group of children that received the ExeFun-READ intervention. In terms of executive functioning, the improvement only extended to switching fluency. [ABSTRACT FROM AUTHOR]

The growing field of family language policies (FLPs), defined as overt and explicit planning in relation to language use among family members, has garnered increasing interest. FLPs influence child–caretaker interactions and are closely linked to child language development and acquisition. This study investigates the impact of FLPs on children's proficiency in their heritage language (HL). Employing a multi-method approach, we conducted semi-structured interviews with 53 multilingual parents to explore their beliefs, ideologies, and language management within the family context. Concurrently, their children were administered standardized tasks in their heritage language (HL) to assess receptive vocabulary skills and morphosyntactic comprehension. Our findings indicate that parents' perceived value of the HL significantly correlates with their children's language performance, going beyond the influence of reported domestic language usage. [ABSTRACT FROM AUTHOR]

Background: Epilepsy stands as an intricate disorder of the central nervous system, subject to the influence of diverse risk factors and a significant genetic predisposition. Within the pathogenesis of temporal lobe epilepsy (TLE), the apoptosis of neurons and glial cells in the brain assumes pivotal importance. The identification of differentially expressed apoptosis-related genes (DEARGs) emerges as a critical imperative, providing essential guidance for informed treatment decisions. Methods: We obtained datasets related to epilepsy, specifically GSE168375 and GSE186334. Utilizing differential expression analysis, we identified a set of 249 genes exhibiting significant variations. Subsequently, through an intersection with apoptosis-related genes, we pinpointed 16 genes designated as differentially expressed apoptosis-related genes (DEARGs). These DEARGs underwent a comprehensive array of analyses, including enrichment analyses, biomarker selection, disease classification modeling, immune infiltration analysis, prediction of miRNA and transcription factors, and molecular docking analysis. Results: In the epilepsy datasets examined, we successfully identified 16 differentially expressed apoptosis-related genes (DEARGs). Subsequent validation in the external dataset GSE140393 revealed the diagnostic potential of five biomarkers (CD38, FAIM2, IL1B, PAWR, S100A8) with remarkable accuracy, exhibiting an impressive area under curve (AUC) (The overall AUC of the model constructed by the five key genes was 0.916, and the validation set was 0.722). Furthermore, a statistically significant variance (p < 0.05) was observed in T cell CD4 naive and eosinophil cells across different diagnostic groups. Exploring interaction networks uncovered intricate connections, including gene-miRNA interactions (164 interactions involving 148 miRNAs), gene-transcription factor (TF) interactions (22 interactions with 20 TFs), and gene-drug small molecule interactions (15 interactions involving 15 drugs). Notably, IL1B and S100A8 demonstrated interactions with specific drugs. Conclusion: In the realm of TLE, we have successfully pinpointed noteworthy differentially expressed apoptosis-related genes (DEARGs), including CD38, FAIM2, IL1B, PAWR, and S100A8. A comprehensive understanding of the implications associated with these identified genes not only opens avenues for advancing our comprehension of the underlying pathophysiology but also bears considerable potential in guiding the development of innovative diagnostic methodologies and therapeutic interventions for the effective management of epilepsy in the future. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma is an aggressive cancer type with one of the lowest survival rates due to late diagnosis and the absence of effective treatments. A better understanding of PDAC biology will help researchers to discover the Achilles' heel of cancer cells. In that regard, our research team investigated the function of an emerging oncoprotein known as myoferlin. Myoferlin is overexpressed in PDAC and its silencing/targeting has been shown to affect cancer cell proliferation, migration, mitochondrial dynamics and metabolism. Nevertheless, our comprehension of myoferlin functions in cells remains limited. In this study, we aimed to understand the molecular mechanism linking myoferlin silencing to mitochondrial dynamics. Methods: Experiments were performed on two pancreas cancer cell lines, Panc-1 and MiaPaCa-2. Myoferlin localization on mitochondria was evaluated by immunofluorescence, proximity ligation assay, and cell fractionation. The presence of myoferlin in mitochondria-associated membranes was assessed by cell fractionation and its function in mitochondrial calcium transfer was evaluated using calcium flow experiments, proximity ligation assays, co-immunoprecipitation, and timelapse fluorescence microscopy in living cells. Results: Myoferlin localization on mitochondria was investigated. Our results suggest that myoferlin is unlikely to be located on mitochondria. Instead, we identified myoferlin as a new component of mitochondria-associated membranes. Its silencing significantly reduces the mitochondrial calcium level upon stimulation, probably through myoferlin interaction with the inositol 1,4,5-triphosphate receptors 3. Conclusions: For the first time, myoferlin was specifically demonstrated to be located in mitochondria-associated membranes where it participates to calcium flow. We hypothesized that this function explains our previous results on mitochondrial dynamics. This study improves our comprehension of myoferlin localization and function in cancer biology. [ABSTRACT FROM AUTHOR]

Far-red light photoacclimation, or FaRLiP, is a facultative response exhibited by some cyanobacteria that allows them to absorb and utilize lower energy light (700-800 nm) than the wavelengths typically used for oxygenic photosynthesis (400-700 nm). During this process, three essential components of the photosynthetic apparatus are altered: photosystem I, photosystem II, and the phycobilisome. In all three cases, at least some of the chromophores found in these pigmentprotein complexes are replaced by chromophores that have red-shifted absorbance relative to the analogous complexes produced in visible light. Recent structural and spectroscopic studies have elucidated important features of the two photosystems when altered to absorb and utilize far-red light, but much less is understood about the modified phycobiliproteins made during FaRLiP. We used single-particle, cryo-EM to determine the molecular structure of a phycobiliprotein core complex comprising allophycocyanin variants that absorb far-red light during FaRLiP in the marine cyanobacterium Synechococcus sp. PCC 7335. The structure reveals the arrangement of the numerous red-shifted allophycocyanin variants and the probable locations of the chromophores that serve as the terminal emitters in this complex. It also suggests how energy is transferred to the photosystem II complexes produced during FaRLiP. The structure additionally allows comparisons with other previously studied allophycocyanins to gain insights into how phycocyanobilin chromophores can be tuned to absorb far-red light. These studies provide new insights into how far-red light is harvested and utilized during FaRLiP, a widespread cyanobacterial photoacclimation mechanism. [ABSTRACT FROM AUTHOR]

This paper examines the relevance of the sentence concept to the understanding of three types of implicitness (presupposition, conversational implicatures, irony). Our experimental protocol involved 105 children (aged 6 to 11) and 82 adults who were asked to read short texts composed of a context about some characters and a target sentence conveying one of the three implicit contents. After reading, children and adults had to answer a comprehension yes-no question and indicate the segments from the text that helped them answer the question. Results showed a difference between the three types of implicitness, with presupposition being detected and understood at a subsentential level, whereas implicatures and irony come under extrasentential level requiring the context to be taken into account. Referring to sentence as a unit of meaning does not seem relevant as soon as understanding is not limited to the literal meaning of what is written, but also concerns what is meant by the text. [ABSTRACT FROM AUTHOR]

This article is an editorial that discusses the neural mechanisms of language and cognitive performance in individuals with neurodevelopmental disorders, specifically autism. The editorial highlights the challenges that individuals with autism face in language comprehension, auditory processing, expressive language, executive functions, intellectual functioning, and social cognition. The research topic aims to expand the understanding of language and cognitive skills in individuals with autism through various methodological approaches. The article also presents several studies that investigate the relationship between executive functioning and autism symptomatology, cortical auditory processing and verbal communication abilities, embodied language comprehension skills, and language, cognitive, and sensory profiles in individuals with autism and epilepsy. Additionally, the article explores the reading comprehension skills of children with autism and the impact of decoding, fluency, morphological and syntactic, and metalinguistic skills on reading comprehension. The overall findings highlight the neurodevelopmental differences in individuals with autism and emphasize the importance of targeting domain-specific cognitive, sensory, and linguistic disruptions to improve their everyday functioning. [Extracted from the article]

Metaphor affects how people focus, remember, and process information and significantly influences children's language development. The study explored metaphorical comprehension by Chinese children of different ages (5-8 years). We collected response times and accuracy rates when they processed metaphorical and literal sentences with the graded salience. Linear mixed-effects modeling showed that Chinese children's metaphorical ability improved with age. Subsequent analysis found that the perception period of metaphorical knowledge was at age 5, the development stage of metaphorical knowledge was at age 6 and 7, and the rational decision period of metaphorical ability was at age 8. After 8-year-old, children can invoke the knowledge of the intention schema while activating the source domain, and this knowledge can be automatically and quickly mapped to the target domain. Meanwhile, language development and cognitive processing influenced the metaphorical comprehension of Chinese children, especially children of 8 years of age who had the highest correct rate and the shortest reaction time to process low-saliency metaphorical sentences, while 5-year-old children had the highest accuracy in high-saliency metaphorical sentence and 6-year-old children got the longest reaction time to process sentence in high-saliency metaphor. This study may provide evidence for improving and training metaphor comprehension in children with special needs such as those with an autism spectrum disorder. [ABSTRACT FROM AUTHOR]

Primary liver cancer, which is scientifically referred to as hepatocellular carcinoma (HCC), is a significant concern in the field of global health. It has been demonstrated that conventional chemotherapy, chemo-hormonal therapy, and conformal radiotherapy are ineffective against HCC. New therapeutic approaches are thus urgently required. Identifying single or multiple mutations in genes associated with invasion, metastasis, apoptosis, and growth regulation has resulted in a more comprehensive comprehension of the molecular genetic underpinnings of malignant transformation, tumor advancement, and host interaction. This enhanced comprehension has notably propelled the development of novel therapeutic agents. Therefore, gene therapy (GT) holds great promise for addressing the urgent need for innovative treatments in HCC. However, the complexity of HCC demands precise and effective therapeutic approaches. The adeno-associated virus (AAV) distinctive life cycle and ability to persistently infect dividing and nondividing cells have rendered it an alluring vector. Another appealing characteristic of the wild-type virus is its evident absence of pathogenicity. As a result, AAV, a vector that lacks an envelope and can be modified to transport DNA to specific cells, has garnered considerable interest in the scientific community, particularly in experimental therapeutic strategies that are still in the clinical stage. AAV vectors emerge as promising tools for HCC therapy due to their non-immunogenic nature, efficient cell entry, and prolonged gene expression. While AAV-mediated GT demonstrates promise across diverse diseases, the current absence of ongoing clinical trials targeting HCC underscores untapped potential in this context. Furthermore, gene transfer through hepatic AAV vectors is frequently facilitated by GT research, which has been propelled by several congenital anomalies affecting the liver. Notwithstanding the enthusiasm associated with this notion, recent discoveries that expose the integration of the AAV vector genome at double-strand breaks give rise to apprehensions regarding their enduring safety and effectiveness. This review explores the potential of AAV vectors as versatile tools for targeted GT in HCC. In summation, we encapsulate the multifaceted exploration of AAV vectors in HCC GT, underlining their transformative potential within the landscape of oncology and human health. [ABSTRACT FROM AUTHOR]

Background: Sexually polymorphic cognition (SPC) results from the interaction between biological (birth-assigned sex (BAS), sex hormones) and socio-cultural (gender identity, gender roles, sexual orientation) factors. The literature remains quite mixed regarding the magnitude of the effects of these variables. This project used a battery of classic cognitive tests designed to assess the influence of sex hormones on cognitive performance. At the same time, we aimed to assess the inter-related and respective effects that BAS, sex hormones, and gender-related factors have on SPC. Methods: We recruited 222 adults who completed eight cognitive tasks that assessed a variety of cognitive domains during a 150-min session. Subgroups were separated based on gender identity and sexual orientation and recruited as follows: cisgender heterosexual men (n = 46), cisgender non-heterosexual men (n = 36), cisgender heterosexual women (n = 36), cisgender non-heterosexual women (n = 38), gender diverse (n = 66). Saliva samples were collected before, during, and after the test to assess testosterone, estradiol, progesterone, cortisol, and dehydroepiandrosterone. Psychosocial variables were derived from self-report questionnaires. Results: Cognitive performance reflects sex and gender differences that are partially consistent with the literature. Interestingly, biological factors seem to better explain differences in male-typed cognitive tasks (i.e., spatial), while psychosocial factors seem to better explain differences in female-typed cognitive tasks (i.e., verbal). Conclusion: Our results establish a better comprehension of SPC over and above the effects of BAS as a binary variable. We highlight the importance of treating sex as a biological factor and gender as a socio-cultural factor together since they collectively influence SPC. Plain Language Summary: Many studies show sex differences in cognitive abilities. In general, women outperform men in verbal tasks and fine motor skills, while men outperform women in spatial orientation and mental rotation tasks. These differences underlie research on sexually polymorphic cognition, a concept influenced by sex hormones (estradiol, progesterone, and testosterone) as well as birth-assigned sex. In addition to these biological factors, socio-cultural gender factors such as gender identity (the gender we feel and embody), gender roles (masculine and feminine expressions based on stereotypes), as well as sexual orientation are all known to influence cognition as well. We provide a broader understanding by accounting for both sex and gender factors. Our team recruited 222 adults separated into 5 sub-groups based on birth-assigned sex, gender identity, and sexual orientation. Each participant completed eight sexually polymorphic cognitive tasks. In this 150-min experimental protocol, saliva samples were collected before, during, and after the test to assess testosterone, estradiol, progesterone, cortisol, and dehydroepiandrosterone. Psychosocial variables were derived from self-report questionnaires. Results showed that spatial cognition was better explained by biological sex factors, while verbal cognition was better explained by socio-cultural gender factors. Taken together, our findings demonstrate the importance of considering sex-based and gender-based factors collectively and, respectively, when studying sex differences in cognition. Highlights: Sex differences in cognition have been extensively studied but remain unclear Incorporating sex and gender factors in cognitive studies is essential Inclusion of sexual and gender diversity further explain cognitive sex differences Contribution of each sex and gender factor depend on the cognitive function observed Spatial cognition appears more sexed, while verbal cognition appears more gendered. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationships between screen exposure, parent-child interactions and comprehension in 8-month-old infants, and to examine whether shared viewing and parent-child conversation during screen exposure may play mediating role in that relationships. Methods: The sample included 437 infants aged 8 months from the Children's Health Department of Guiyang Maternal and Child Health Hospital during January 2022 to February 2023. The use of electronic screen devices was assessed using a screen exposure questionnaire. The Brigance Parent-child interactions Scale was used to assess parent-child interactions and the Putonghua Communicative Development Inventory (PCDI) scale was used to assess infants' word comprehension. Results: 48.7% of infants were found to be using screens 1–2 days per week. There was a significant difference (p < 0.05) in the PCDI-comprehension scores of screen-exposed infants compared to non-screen-exposed infants. Shared viewing and parent-child conversation during screen exposure were positively associated with parent-child interactions (p < 0.05). Mediation analysis revealed that parent-child conversation fully mediated between screen exposure and PCDI-comprehension, but partially mediated between parent-child interactions and PCDI-comprehension. Conclusions: Shared viewing and parent-child conversation during screen exposure may mediate between screen exposure and comprehension development. Shared viewing, parent-child conversation and parent-child interactions may be protective factors for screen exposure in comprehension development. Suggests that parents should accompany and communicate with their children when they use electronic screen devices to reduce the negative impact of screen exposure on children's comprehension. [ABSTRACT FROM AUTHOR]

Lymphovascular space invasion (LVSI) is the presence of tumor emboli in the endothelial-lined space at the tumor body's invasive edge. LVSI is one of three Sedlis criteria components—a prognostic tool for early cervical cancer (CC)—essential for indicating poor prognosis, such as lymph node metastasis, distant metastasis, or shorter survival rate. Despite its clinical significance, an in-depth comprehension of the molecular mechanisms or immune dynamics underlying LVSI in CC remains elusive. Therefore, this study investigated tumor-immune microenvironment (TIME) dynamics of the LVSI-positive group in CC. RNA sequencing included formalin-fixed paraffin-embedded (FFPE) slides from 21 CC patients, and differentially expressed genes (DEGs) were analyzed. Functional analysis and immune deconvolution revealed aberrantly enriched PI3K/Akt pathway activation and a heterogenic immune composition with a low abundance of regulatory T cells (Treg) between LVSI-positive and LVSI-absent groups. These findings improve the comprehension of LSVI TIME and immune mechanisms, benefiting targeted LVSI therapy for CC. [ABSTRACT FROM AUTHOR]

Sub-micron particles are ubiquitous in the indoor environment, especially during wildfire smoke episodes, and have a higher impact on human health than larger particles. Conventional fibrous air filters installed in heating, ventilation, and air conditioning (HVAC) systems play an important role in controlling indoor air quality by removing various air pollutants, including particulate matter (PM). However, it is evident that the removal efficiency of wildfire smoke PM and its effect on filter performance is significantly under-studied. This study delves into the size-specific removal efficiency of pine needle smoke, a representative of wildfire smoke and emissions. We test an array of filter media with minimum efficiency reporting values (MERV) spanning 11–15. Both size-resolved particle number concentrations and mass concentrations were measured using an Optical Particle Sizer (OPS, TSI, Inc.) and a Scanning Mobility Particle Sizer (SMPS, TSI, Inc.). Furthermore, we characterize the filter media morphology and smoke particles deposited on filter fibers using Scanning Electron Microscopy (SEM) to gain insights into the interaction dynamics of these particles. Our findings add to the comprehension of the relationship between MERV designations and smoke removal efficiency. Such insight can inform standards and guidelines and equip decision-makers with the knowledge needed to initiate measures for mitigating the impact of air pollution, specifically on the indoor environment. [ABSTRACT FROM AUTHOR]

Sexual differentiation is an important developmental phenomenon in cucurbits that directly affects fruit yield. The natural existence of multiple flower types in melon offers an inclusive structure for studying the molecular basis of sexual differentiation. The current study aimed to identify and characterize the molecular network involved in sex determination and female development in melon. Male and female pools separated by the F2 segregated generation were used for sequencing. The comparative multi-omics data revealed 551 DAPs and 594 DEGs involved in multiple pathways of melon growth and development, and based on functional annotation and enrichment analysis, we summarized four biological process modules, including ethylene biosynthesis, flower organ development, plant hormone signaling, and ubiquitinated protein metabolism, that are related to female development. Furthermore, the detailed analysis of the female developmental regulatory pathway model of ethylene biosynthesis, signal transduction, and target gene regulation identified some important candidates that might have a crucial role in female development. Two CMTs ((cytosine-5)-methyltransferase), one AdoHS (adenosylhomocysteinase), four ACSs (1-aminocyclopropane-1-carboxylic acid synthase), three ACOs (ACC oxidase), two ARFs (auxin response factor), four ARPs (auxin-responsive protein), and six ERFs (Ethylene responsive factor) were identified based on various female developmental regulatory models. Our data offer new and valuable insights into female development and hold the potential to offer a deeper comprehension of sex differentiation mechanisms in melon. [ABSTRACT FROM AUTHOR]

Whether non-case-marked objects with and without the numeral bir in Turkish have the same structural properties or not has been a topic of discussion for decades. This study aims to contribute to this discussion with experimental data that compares the comprehension of these object types along with their accusative-marked indefinite counterparts in terms of their scope with respect to negation by four-, five-, and six-year-old children as well as adults. The results suggest that both non-case-marked objects with and without bir contrast with accusative-marked indefinite objects and have a narrow scope with respect to negation in adults' speech. However, bir can still have a main effect on the interpretation of the objects, just like the accusative case, and unlike non-case-marked objects without bir, objects with bir may scope over negation. Children treat all object types alike at age four and distinguish objects with and without bir at age five. These findings are compatible with an account that assumes different structures for two types of non-case-marked objects. [ABSTRACT FROM AUTHOR]

Cachexia is a devastating pathology that worsens the quality of life and antineoplastic treatment outcomes of oncologic patients. Herein, we report that the secretome from murine colon carcinoma CT26 induces cachectic features in both murine and human adipocytes that are associated with metabolic alterations such as enhanced lactate production and decreased oxygen consumption. The use of oxamate, which inhibits lactate dehydrogenase activity, hinders the effects induced by CT26 secretome. Interestingly, the CT26 secretome elicits an increased level of lactate dehydrogenase and decreased expression of adiponectin. These modifications are driven by the STAT3 signalling cascade since the inhibition of STAT3 with WP1066 impedes the formation of the cachectic condition and the alteration of lactate dehydrogenase and adiponectin levels. Collectively, these findings show that STAT3 is responsible for the altered lactate dehydrogenase and adiponectin levels that, in turn, could participate in the worsening of this pathology and highlight a step forward in the comprehension of the mechanisms underlying the onset of the cachectic condition in adipocytes. [ABSTRACT FROM AUTHOR]

Developmental Language Disorder (DLD), present in 2 out of every 30 children, affects primarily oral language abilities and development in the absence of associated biomedical conditions. We report the first experimental study that examines relative clause (RC) comprehension accuracy and processing (via looking preference) in Cantonese-speaking children with and without DLD, testing the predictions from competing domain-specific versus domain-general theoretical accounts. We compared children with DLD (N = 22) with their age-matched typically-developing (TD) children (AM-TD, N = 23) aged 6;6–9;7 and language-matched (and younger) TD children (YTD, N = 21) aged 4;7–7;6, using a referent selection task. Within-subject factors were: RC type (subject-RCs (SRCs) versus object-RCs (ORCs); relativizer (classifier (CL) versus relative marker ge3 RCs). Accuracy measures and looking preference to the target were analyzed using generalized linear mixed effects models. Results indicated Cantonese children with DLD scored significantly lower than their AM-TD peers in accuracy and processed RCs significantly slower than AM-TDs, but did not differ from the YTDs on either measure. Overall, while the results revealed evidence of a SRC advantage in the accuracy data, there was no indication of additional difficulty associated with ORCs in the eye-tracking data. All children showed a processing advantage for the frequent CL relativizer over the less frequent ge3 relativizer. These findings pose challenges to domain-specific representational deficit accounts of DLD, which primarily explain the disorder as a syntactic deficit, and are better explained by domain-general accounts that explain acquisition and processing as emergent properties of multiple converging linguistic and non-linguistic processes. [ABSTRACT FROM AUTHOR]

Protein palmitoylation, a cellular process occurring at the membrane-cytosol interface, is orchestrated by members of the DHHC enzyme family and plays a pivotal role in regulating various cellular functions. The M2 protein of the influenza virus, which is acylated at a membrane-near amphiphilic helix serves as a model for studying the intricate signals governing acylation and its interaction with the cognate enzyme, DHHC20. We investigate it here using both experimental and computational assays. We report that altering the biophysical properties of the amphiphilic helix, particularly by shortening or disrupting it, results in a substantial reduction in M2 palmitoylation, but does not entirely abolish the process. Intriguingly, DHHC20 exhibits an augmented affinity for some M2 mutants compared to the wildtype M2. Molecular dynamics simulations unveil interactions between amino acids of the helix and the catalytically significant DHHC and TTXE motifs of DHHC20. Our findings suggest that the binding of M2 to DHHC20, while not highly specific, is mediated by requisite contacts, possibly instigating the transfer of fatty acids. A comprehensive comprehension of protein palmitoylation mechanisms is imperative for the development of DHHC-specific inhibitors, holding promise for the treatment of diverse human diseases. [ABSTRACT FROM AUTHOR]

This research shows that improved scientific reasoning and application of concepts occurred when creating and viewing student-crafted digital storytelling projects. By utilizing digital storytelling projects to showcase course competencies in an undergraduate biology course, students were able to apply subject matter outside the classroom. In this post hoc analysis of pretest and posttest scores from a two-year Florida college, significant results with medium effect sizes were shown for classes engaged in digital storytelling projects. It was determined that age was not a significant factor. [ABSTRACT FROM AUTHOR]

In plants, ARRs-B transcription factors play a crucial role in regulating cytokinin signal transduction, abiotic stress resistance, and plant development. A number of adverse environmental conditions have caused severe losses for the pepper (Capsicum annuum L.)--a significant and economically important vegetable. Among the transcription factors of the type B-ARRs family, multiple members have different functions. In pepper, only a few members of the ARRs-B family have been reported and characterized. The current study aimed to characterize ARRs-B transcription factors in C. annuum, including phylogenetic relationships, gene structures, protein motif arrangement, and RT-qPCR expression analyses and their role in salinity stress. In total, ten genes encode CaARRs-B transcription factors (CaARR1 to CaARR10) from the largest subfamily of type-B ARRs were identified in C. annum. The genome-wide analyses of the CaARRs-B family in C. annuum were performed based on the reported ARRs-B genes in Arabidopsis. An analysis of homologous alignments of candidate genes, including their phylogenetic relationships, gene structures, conserved domains, and qPCR expression profiles, was conducted. In comparison with other plant ARRs-B proteins, CaARRs-B proteins showed gene conservation and potentially specialized functions. In addition, tissue-specific expression profiles showed that CaARRs-B genes were differentially expressed, suggesting functionally divergent. CaARRs-B proteins had a typical conserved domain, including AAR-like (pfam: PF00072) and Myb DNA binding (pfam: PF00249) domains. Ten of the CaARRs-B genes were asymmetrically mapped on seven chromosomes in Pepper. Additionally, the phylogenetic tree of CaARRs-B genes from C. annuum and other plant species revealed that CaARRs-B genes were classified into four clusters, which may have evolved conservatively. Further, using quantitative real-time qRT-PCR, the study assessed the expression patterns of CaARRs-B genes in Capsicum annuum seedlings subjected to salt stress. The study used quantitative real-time qRT-PCR to examine CaARRs-B gene expression in Capsicum annuum seedlings under salt stress. Roots exhibited elevated expression of CaARR2 and CaARR9, while leaves showed decreased expression for CaARR3, CaARR4, CaARR7, and CaARR8. Notably, no amplification was observed for CaARR10. This research sheds light on the roles of CaARRs-B genes in pepper's response to salinity stress. These findings enrich our comprehension of the functional implications of CaARRs-B genes in pepper, especially in responding to salinity stress, laying a solid groundwork for subsequent in-depth studies and applications in the growth and development of Capsicum annuum. [ABSTRACT FROM AUTHOR]

Summary: In recent years, single‐cell genomics, coupled to imaging techniques, have become the state‐of‐the‐art approach for characterising biological systems. In plant sciences, a variety of tissues and species have been profiled, providing an enormous quantity of data on cell identity at an unprecedented resolution, but what biological insights can be gained from such data sets? Using recently published studies in plant sciences, we will highlight how single‐cell technologies have enabled a better comprehension of tissue organisation, cell fate dynamics in development or in response to various stimuli, as well as identifying key transcriptional regulators of cell identity. We discuss the limitations and technical hurdles to overcome, as well as future directions, and the promising use of single‐cell omics to understand, predict, and manipulate plant development and physiology. [ABSTRACT FROM AUTHOR]

The Eph kinases are the largest receptor tyrosine kinases (RTKs) family in humans. PC3 human prostate adenocarcinoma cells are a well-established model for studying Eph–ephrin pharmacology as they naturally express a high level of EphA2, a promising target for new cancer therapies. A pharmacological approach with agonists did not show significant efficacy on tumor growth in prostate orthotopic murine models, but reduced distal metastasis formation. In order to improve the comprehension of the pharmacological targeting of Eph receptors in prostate cancer, in the present work, we investigated the efficacy of Eph antagonism both in vitro and in vivo, using UniPR1331, a small orally bioavailable Eph–ephrin interaction inhibitor. UniPR1331 was able to inhibit PC3 cells' growth in vitro in a dose-dependent manner, affecting the cell cycle and inducing apoptosis. Moreover, UniPR1331 promoted the PC3 epithelial phenotype, downregulating epithelial mesenchymal transition (EMT) markers. As a consequence, UniPR1331 reduced in vitro PC3 migration, invasion, and vasculomimicry capabilities. The antitumor activity of UniPR1331 was confirmed in vivo when administered alone or in combination with cytotoxic drugs in PC3-xenograft mice. Our results demonstrated that Eph antagonism is a promising strategy for inhibiting prostate cancer growth, especially in combination with cytotoxic drugs. [ABSTRACT FROM AUTHOR]