Complexity Matters: Normalization to Prototypical Viewpoint Induces Memory Distortion along the Vertical Axis of Scenes.

Scene memory is prone to systematic distortions potentially arising from experience with the external world. Boundary transformation, a well-known memory distortion effect along the near-far axis of the three-dimensional space, represents the observer's erroneous recall of scenes' viewing distance. Researchers argued that normalization to the prototypical viewpoint with the high-probability viewing distance influenced this phenomenon. Herein, we hypothesized that the prototypical viewpoint also exists in the vertical angle of view (AOV) dimension and could cause memory distortion along scenes' vertical axis. Human subjects of both sexes were recruited to test this hypothesis, and two behavioral experiments were conducted, revealing a systematic memory distortion in the vertical AOV in both the forced choice (n = 79) and free adjustment (n = 30) tasks. Furthermore, the regression analysis implied that the complexity information asymmetry in scenes' vertical axis and the independent subjective AOV ratings from a large set of online participants (n = 1,208) could jointly predict AOV biases. Furthermore, in a functional magnetic resonance imaging experiment (n = 24), we demonstrated the involvement of areas in the ventral visual pathway (V3/V4, PPA, and OPA) in AOV bias judgment. Additionally, in a magnetoencephalography experiment (n = 20), we could significantly decode the subjects' AOV bias judgments ∼140 ms after scene onset and the low-level visual complexity information around the similar temporal interval. These findings suggest that AOV bias is driven by the normalization process and associated with the neural activities in the early stage of scene processing.

Artificial intelligence classifies primary progressive aphasia from connected speech.

Neurodegenerative dementia syndromes, such as Primary Progressive Aphasias (PPA), have traditionally been diagnosed based in part on verbal and nonverbal cognitive profiles. Debate continues about whether PPA is best divided into three variants and also regarding the most distinctive linguistic features for classifying PPA variants. In this cross-sectional study, we first harnessed the capabilities of artificial intelligence (AI) and Natural Language Processing (NLP) to perform unsupervised classification of short, connected speech samples from 78 PPA patients. We then used NLP to identify linguistic features that best dissociate the three PPA variants. Large Language Models (LLMs) discerned three distinct PPA clusters, with 88.5% agreement with independent clinical diagnoses. Patterns of cortical atrophy of three data-driven clusters corresponded to the localization in the clinical diagnostic criteria. In the subsequent supervised classification, seventeen distinctive features emerged, including the observation that separating verbs into high and low-frequency types significantly improves classification accuracy. Using these linguistic features derived from the analysis of short, connected speech samples, we developed a classifier that achieved 97.9% accuracy in classifying the four groups (three PPA variants and healthy controls). The data-driven section of this study showcases the ability of LLMs to find natural partitioning in the speech of patients with PPA consistent with conventional variants. In addition, the work identifies a robust set of language features indicative of each PPA variant, emphasizing the significance of dividing verbs into high and low-frequency categories. Beyond improving diagnostic accuracy, these findings enhance our understanding of the neurobiology of language processing.

Parafoveal vision reveals qualitative differences between fusiform face area and parahippocampal place area.

The center-periphery visual field axis guides early visual system organization with enhanced resources devoted to central vision leading to reduced peripheral performance relative to that of central vision (i.e., behavioral eccentricity effect) for many visual functions. The center-periphery organization extends to high-order visual cortex where, for example, the well-studied face-sensitive fusiform face area (FFA) shows sensitivity to central vision and the place-sensitive parahippocampal place area (PPA) shows sensitivity to peripheral vision. As we have recently found that face perception is more sensitive to eccentricity than place perception, here we examined whether these behavioral findings reflect differences in FFA's and PPA's sensitivities to eccentricity. We assumed FFA would show higher sensitivity to eccentricity than PPA would, but that both regions' modulation by eccentricity would be invariant to the viewed category. We parametrically investigated (fMRI, n = 32) how FFA's and PPA's activations are modulated by eccentricity (≤8°) and category (upright/inverted faces/houses) while keeping stimulus size constant. As expected, FFA showed an overall higher sensitivity to eccentricity than PPA. However, both regions' activation modulations by eccentricity were dependent on the viewed category. In FFA, a reduction of activation with growing eccentricity ("BOLD eccentricity effect") was found (with different amplitudes) for all categories. In PPA however, qualitatively different BOLD eccentricity effect modulations were found (e.g., at 8° mild BOLD eccentricity effect for houses but a reverse BOLD eccentricity effect for faces and no modulation for inverted faces). Our results emphasize that peripheral vision investigations are critical to further our understanding of visual processing.

Positive effects of speech and language therapy group interventions in primary progressive aphasia: A systematic review.

BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative condition characterised by a prominent and progressive deterioration in language abilities, which significantly impacts quality of life and interpersonal relationships. Speech and language therapy plays a crucial role in offering interventions. Group intervention is one mode of delivery that could benefit communication functioning and overall wellbeing of people with PPA (pwPPA) and their care partners. Group interventions are also more efficient than one-to-one intervention and may facilitate peer support. AIMS: The aim of this review was to systematically evaluate the current evidence for the effectiveness of speech and language therapy groups for pwPPA and their care partners. Specifically, this paper considered three questions: 1.What evidence-based speech and language therapy groups for pwPPA and their care partners have been reported to date? 2.Are group communication interventions effective in improving quality of life and communication function for pwPPA and their care partners? 3.Are group communication interventions that are designed for people with communication difficulties of other aetiologies (such as stroke) effective for pwPPA? In addition, this review aimed to describe the structure and content of groups, including aims, disciplines involved, size and frequency of group meetings, and outcome measures. METHODS: MEDLINE, CINAHL and PsycINFO were used to retrieve articles of interest. A total of 10 studies published between 2009 and 2022 met the eligibility criteria and therefore were included in this study. Data were extracted from the articles regarding the structure and content of groups. MAIN CONTRIBUTION: Although evidence is currently limited, results suggest that speech and language therapy group intervention can improve specific linguistic processes, the use of communication strategies and psychosocial well-being. The importance of multidisciplinary input and care partners' involvement in groups was highlighted, along with the benefits of creative non-verbal activities as tools for self-expression. There is also initial evidence that telehealth group provision and one-off group sessions may be feasible and can benefit psychosocial well-being. Lastly, intentional recruitment and explicit education on different aphasia types are described as important when pwPPA participate in groups with mixed diagnoses. CONCLUSIONS: The literature on speech and language therapy group interventions for PPA shows promise of positive effects on communication function and psychosocial well-being of both pwPPA and their care partners. Speech and language therapists can consider these published interventions when designing and implementing similar groups, but more robust evidence is required to confirm the relative effectiveness of this approach. WHAT THIS PAPER ADDS: What is already known on this subject Speech pathology led group intervention shows some promise in benefitting communication functioning and overall well-being of pwPPA and their carers, but there has been no systematic evaluation of all the evidence regarding the efficacy of speech and language therapy led groups. Establishing feasibility, acceptability and efficacy of speech and language therapy group interventions for pwPPA and their carers may present a valuable addition for managing this progressive language disability. What this paper adds to existing knowledge Although evidence is currently limited, results from this systematic review suggest that speech and language therapy led group intervention can improve specific linguistic processes, the use of communication strategies and psychosocial well-being for pwPPA and their carers. The importance of multidisciplinary input and carers' involvement in groups was highlighted, along with the benefits of creative non-verbal activities as tools for self-expression. There is also initial evidence that telehealth group provision for carers may be feasible and can benefit psychosocial wellbeing. Lastly, intentional recruitment and explicit education on different aphasia types are described as important when pwPPA participate in groups with mixed diagnoses. What are the potential or actual clinical implications of this work? A synthesis of the evidence base for speech and language therapy led PPA groups, as well as a description of the group components and formats, will be valuable for clinical service planning, and will guide future examination of group options for pwPPA and their carers. Speech and language therapists can also consider the research findings from this systematic review when designing and implementing similar groups in their local context.

Identification of PPA1 inhibitor candidates for potential repurposing in cancer medicine.

Inorganic pyrophosphatase 1 (PPA1) is pivotal to cellular metabolism as it facilitates the hydrolysis of PPi-a by-product of various metabolic processes that influence cell growth and differentiation. Overexpression of PPA1 enzyme has been linked to diminished patient survival and was shown to influence tumor cell dynamics, thereby positioning it as a potential therapy target for a variety of cancers including colorectal cancer, diffuse large B-cell lymphoma, and lung adenocarcinoma. Despite this therapeutic promise, there are no known inhibitors of PPA1 as of today. In this study, we searched for potential PPA1 inhibitors using a molecular docking screen of 30 470 compounds with a history of clinical trials and/or US Food and Drug Administration approval. We specifically targeted the active pocket that coincides with the established catalytic domain. Our screen identified promising hits, which we further subjected to ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering. Subsequent molecular dynamics (MD) analyses were conducted on devazepide, quinotolast, and tarazepide-the three substances that successfully navigated all filters. MD analyses reinforced the stability of the protein-ligand complexes and confirmed ligand binding, as substantiated by our root mean square deviation, radius of gyration and secondary structures of proteins analyses. Furthermore, Molecular Mechanics Poisson-Boltzmann Surface Area calculations post-MD identified devazepide and quinotolast as showing higher binding affinities; being supported by principal component analysis, free energy landscape, and dynamic cross-correlation matrix results. Overall, our study reveals devazepide and quinotolast as potential candidates for PPA1 inhibition which could be considered for repurposing studies that need further experimental validation. These results not only reveal a potential for clinical repurposing for PPA1 inhibition but they also offer valuable insights into the development of future compounds for targeting the crucial PPA1 enzyme.

Cold-inducible PPA1 is critical for the adipocyte browning in mice.

Promoting the thermogenic capacity of brown/beige adipocytes is becoming a promising strategy to counteract obesity and related metabolic diseases. Inorganic pyrophosphatase 1 (PPA1) is an enzyme that catalyzes the hydrolysis of PPi to Pi, and its presence is required for anabolism to take place in cells. Our previous study demonstrated the importance of PPA1 in maintaining adipose tissue function and whole-body metabolic homeostasis. In this study, we found that the expression of PPA1 was positively associated with the thermogenic capacity of brown/beige adipocytes. PPA1+/- mice exhibited less browning capacity in subcutaneous white adipose tissue compared to wild-type mice and also showed apparent cold intolerance. We found that decreased PPA1 abundance may lead to mitochondrial dysfunction and inhibited adipocyte browning both in vivo and in vitro. Furthermore, our study also revealed that PPA1 worked as a new target gene of nuclear respiratory factor 1 (NRF1), a major transcription regulator of mitochondrial biogenesis. Together, our findings indicated an essential role of PPA1 in mitochondrial function and browning in adipocytes and suggested PPA1 as a new therapeutic target for increasing thermogenesis to combat obesity and metabolic diseases.

Access, referral, service provision and management of individuals with primary progressive aphasia: A survey of speech-language therapists in Italy.

BACKGROUND AND OBJECTIVES: In Italy, approximately 650 individuals receive a diagnosis of primary progressive aphasia (PPA) every year. Unfortunately, the frequency with which patients are referred to speech-language services is suboptimal, likely due to skepticism regarding the value of speech-language therapy in the context of neurodegeneration. MATERIALS AND METHODS: We conducted a virtual survey of speech and language therapists (SLTs) across Italy, to collect information about the assessment, intervention and management of patients with PPA. To ensure that as many SLTs as possible received the survey, the Italian Federation of SLTs (Federazione Logopedisti Italiani, FLI) aided in disseminating the survey. RESULTS: In total, 336 respondents participated in the online survey, 140 of whom had previous experience with PPA patients. Respondents indicated having seen a total of 428 PPA patients in the previous 24 months (three patients on average, range: 0-40). SLTs who reported never working with PPA identified underdiagnoses, low referral rates and the rarity of the clinical syndrome as major reasons for their lack of experience with PPA. SLTs with experience working with PPA indicated that patients may not have accessed services because of service dysfunction and geographical barriers. Respondents reported using informal interviews during assessments and tests developed for post-stroke aphasia, while impairment-based/restitutive interventions were utilised most often. CONCLUSION: Findings may serve to inform health policy organisations regarding the current shortcomings and needed recommendations for improving the care of individuals with PPA in Italy. Improving awareness of the utility of rehabilitation among SLTs and other clinical service providers may serve to facilitate access to intervention, which in turn will serve to better support individuals living with PPA. WHAT THIS PAPER ADDS: What is already known on the subject Speech and language therapists (SLTs) play a crucial role in the assessment, diagnosis and treatment of people with primary progressive aphasia (PPA). However, the frequency with which individuals with PPA are referred for speech and language services is suboptimal due to skepticism regarding the value of speech and language therapy in the context of neurodegeneration, the scarcity of SLTs with expertise in the treatment of PPA and the lack of awareness of the SLT role amongst referrers. What this paper adds to existing knowledge In recognition of the lack of published information on the provision of speech and language therapy services and clinicians' approaches to the assessment and treatment of individuals with PPA in Italy, we conducted an online survey to evaluate the current referral patterns for speech and language therapy services and to examine the current barriers to access these services for individuals with PPA in Italy. What are the potential or actual clinical implications of this work? The data presented here support that SLTs view treatment as useful for individuals with PPA and other professional figures and may serve to improve access to intervention, which in turn will serve to better support individuals living with PPA. The results highlight the need to inform health policy organisations about current gaps and aid in developing recommendations for improving the care of individuals with PPA, in order to understand how SLTs can best support individuals with PPA and their families.

Influence of amyloid and diagnostic syndrome on non-traditional memory scores in early-onset Alzheimer's disease.

INTRODUCTION: The Rey Auditory Verbal Learning Test (RAVLT) is a useful neuropsychological test for describing episodic memory impairment in dementia. However, there is limited research on its utility in early-onset Alzheimer's disease (EOAD). We assess the influence of amyloid and diagnostic syndrome on several memory scores in EOAD. METHODS: We transcribed RAVLT recordings from 303 subjects in the Longitudinal Early-Onset Alzheimer's Disease Study. Subjects were grouped by amyloid status and syndrome. Primacy, recency, J-curve, duration, stopping time, and speed score were calculated and entered into linear mixed effects models as dependent variables. RESULTS: Compared with amyloid negative subjects, positive subjects exhibited effects on raw score, primacy, recency, and stopping time. Inter-syndromic differences were noted with raw score, primacy, recency, J-curve, and stopping time. DISCUSSION: RAVLT measures are sensitive to the effects of amyloid and syndrome in EOAD. Future work is needed to quantify the predictive value of these scores. HIGHLIGHTS: RAVLT patterns characterize various presentations of EOAD and EOnonAD Amyloid impacts raw score, primacy, recency, and stopping time Timing-based scores add value over traditional count-based scores.

Investigation of inpatient convalescent rehabilitation outcomes in branch atheromatous disease.

PURPOSE: We investigated inpatient convalescent rehabilitation outcomes of Branch atheromatous disease (BAD). SUBJECTS AND METHODS: The subjects were 116 patients with lenticulostriate artery territory - BAD (LSA-BAD) and 29 with paramedian pontine artery territory - BAD (PPA-BAD). For all patients, the National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM) scores, and Brunnstrom recovery stages (BRS) of the upper limb, fingers, and lower limb were measured on admission and at discharge. RESULTS: There were no significant differences in clinical characteristics on admission between the LSA-BAD and PPA-BAD groups. The neurological severity of PPA-BAD, as measured by the NIHSS, was significantly milder compared with that of LSA-BAD upon admission (p = 0.015) and at discharge (p = 0.001). Patients with LSA-BAD had significantly less improvement in the BRS of the upper limb (p = 0.001), fingers (p < 0.001), and lower limb (p = 0.007) at discharge. Furthermore, they had significantly smaller changes in BRS between admission and discharge for the upper limb (p = 0.033) and fingers (p = 0.014) compared with patients with PPA-BAD. The improvement in BRS for patients with LSA-BAD tended to be limited to two stages; however, both patients with LSA-BAD and PPA-BAD saw sufficient gains in FIM at discharge. CONCLUSION: Rehabilitation outcomes following BAD in the convalescent period should be assessed in terms of improvements in pure-motor hemiparesis and activities of daily living. Furthermore, the disturbance patterns in the corticospinal tract by ischemic stroke lesions may be different between LSA-BAD and PPA-BAD.

Neural Representations in the Prefrontal Cortex Are Task Dependent for Scene Attributes But Not for Scene Categories.

Natural scenes deliver rich sensory information about the world. Decades of research has shown that the scene-selective network in the visual cortex represents various aspects of scenes. However, less is known about how such complex scene information is processed beyond the visual cortex, such as in the prefrontal cortex. It is also unknown how task context impacts the process of scene perception, modulating which scene content is represented in the brain. In this study, we investigate these questions using scene images from four natural scene categories, which also depict two types of scene attributes, temperature (warm or cold), and sound level (noisy or quiet). A group of healthy human subjects from both sexes participated in the present study using fMRI. In the study, participants viewed scene images under two different task conditions: temperature judgment and sound-level judgment. We analyzed how these scene attributes and categories are represented across the brain under these task conditions. Our findings show that scene attributes (temperature and sound level) are only represented in the brain when they are task relevant. However, scene categories are represented in the brain, in both the parahippocampal place area and the prefrontal cortex, regardless of task context. These findings suggest that the prefrontal cortex selectively represents scene content according to task demands, but this task selectivity depends on the types of scene content: task modulates neural representations of scene attributes but not of scene categories.SIGNIFICANCE STATEMENT Research has shown that visual scene information is processed in scene-selective regions in the occipital and temporal cortices. Here, we ask how scene content is processed and represented beyond the visual brain, in the prefrontal cortex (PFC). We show that both scene categories and scene attributes are represented in PFC, with interesting differences in task dependency: scene attributes are only represented in PFC when they are task relevant, but scene categories are represented in PFC regardless of the task context. Together, our work shows that scene information is processed beyond the visual cortex, and scene representation in PFC reflects how adaptively our minds extract relevant information from a scene.

The role of ventral stream areas for viewpoint-invariant object recognition.

Object constancy is one of the most crucial mechanisms of the human visual system enabling viewpoint invariant object recognition. However, the neuronal foundations of object constancy are widely unknown. Research has shown that the ventral visual stream is involved in processing of various kinds of object stimuli and that several regions along the ventral stream are possibly sensitive to the orientation of an object in space. To systematically address the question of viewpoint sensitive object perception, we conducted a study with stroke patients as well as an fMRI experiment with healthy participants applying object stimuli in several spatial orientations, for example in typical and atypical viewing conditions. In the fMRI experiment, we found stronger BOLD signals and above-chance classification accuracies for objects presented in atypical viewing conditions in fusiform face sensitive and lateral occipito-temporal object preferring areas. In the behavioral patient study, we observed that lesions of the right fusiform gyrus were associated with lower performance in object recognition for atypical views. The complementary results from both experiments emphasize the contributions of fusiform and lateral-occipital areas to visual object constancy and indicate that visual object constancy is particularly enabled through increased neuronal activity and specific activation patterns for objects in demanding viewing conditions.

The representation of shape and texture in category-selective regions of ventral-temporal cortex.

Neuroimaging studies using univariate and multivariate approaches have shown that the fusiform face area (FFA) and parahippocampal place area (PPA) respond selectively to images of faces and places. The aim of this study was to determine the extent to which this selectivity to faces or places is based on the shape or texture properties of the images. Faces and houses were filtered to manipulate their texture properties, while preserving the shape properties (spatial envelope) of the images. In Experiment 1, multivariate pattern analysis (MVPA) showed that patterns of fMRI response to faces and houses in FFA and PPA were predicted by the shape properties, but not by the texture properties of the image. In Experiment 2, a univariate analysis (fMR-adaptation) showed that responses in the FFA and PPA were sensitive to changes in both the shape and texture properties of the image. These findings can be explained by the spatial scale of the representation of images in the FFA and PPA. At a coarser scale (revealed by MVPA), the neural selectivity to faces and houses is sensitive to variation in the shape properties of the image. However, at a finer scale (revealed by fMR-adaptation), the neural selectivity is sensitive to the texture properties of the image. By combining these neuroimaging paradigms, our results provide insights into the spatial scale of the neural representation of faces and places in the ventral-temporal cortex.

Electrophysiological abnormalities as indicators of early-stage pathology in Primary Progressive Aphasia (PPA): A case study in semantic variant PPA.

Language induced and spontaneous oscillatory activity was measured using MEG in a patient with the semantic variant of Primary Progressive Aphasia (svPPA) and 15 healthy controls.The patient showed oscillatory slowing in the left anterior temporal lobe (ATL) that extended into non-atrophied brain tissue in left and right frontal areas. The white matter connections were reduced to the left and right ATL and left frontal regions, exhibiting electrophysiological abnormalities. Altered diffusion metrics in all four language tracts, indicted compromised white matter integrity. Task-related and spontaneous oscillatory abnormalities can indicate early neurodegeneration in svPPA, providing promising targets for intervention.

Pomegranate peel anthocyanins prevent diet-induced obesity and insulin resistance in association with modulation of the gut microbiota in mice.

PURPOSE: Pomegranate peels are rich in anthocyanins. The present study aimed to explore the beneficial effects of pomegranate peel anthocyanins (PPA) on obesity and gut microbiota in mice with high-fat diet (HFD)-induced obesity. METHODS: Specific pathogen-free (SPF) male C57BL/6 J mice were randomly divided into three groups and fed with low-fat diet (LFD, 10% fat energy), HFD (45% fat energy), or HFD supplemented with PPA by intragastric administration for 15 weeks. Body weight and food intake were monitored weekly. The obesity-related biochemical indexes and hepatic gene expression levels were determined. The compositions of the gut microbiota were analyzed by 16S rRNA sequencing, and the association between the gut microbiota and obesity-related indicators was investigated by Spearman correlation analysis. RESULTS: The results showed that the body weight gain, steatosis scores and insulin resistance index in the PPA group decreased by 27.46%, 56.25%, and 46.07%, respectively, compared to the HFD group. Gene expression analysis indicated that PPA supplement improved the genes expression profiles involved in glucose and lipid metabolism compared with the mice fed HFD alone. Meanwhile, PPA significantly changed the composition of the gut microbiota, which were closely correlated with the obesity-related biomarkers. CONCLUSION: This study suggested that PPA could be a beneficial treatment option for alleviating HFD-induced obesity and related metabolic disorders by targeting microbiota and lipid metabolism.

Distinct representations of spatial and categorical relationships across human scene-selective cortex.

We represent the locations of places (e.g., the coffee shop on 10th Street vs. the coffee shop on Peachtree Street) so that we can use them as landmarks to orient ourselves while navigating large-scale environments. While several neuroimaging studies have argued that the parahippocampal place area (PPA) represents such navigationally relevant information, evidence from other studies suggests otherwise, leaving this issue unresolved. Here we hypothesize that the PPA is, in fact, not well suited to recognize specific landmarks in the environment (e.g., the coffee shop on 10th Street), but rather is involved in recognizing the general category membership of places (e.g., a coffee shop, regardless of its location). Using fMRI multivoxel pattern analysis, we directly test this hypothesis. If the PPA represents landmark information, then it must be able to discriminate between 2 places of the same category, but in different locations. Instead, if the PPA represents general category information (as hypothesized here), then it will not represent the location of a particular place, but only the category of the place. As predicted, we found that the PPA represents 2 buildings from the same category, but in different locations, as more similar than 2 buildings from different categories, but in the same location. In contrast, another scene-selective region of cortex, the retrosplenial complex (RSC), showed the exact opposite pattern of results. Such a double dissociation suggests distinct neural systems involved in categorizing and navigating our environment, including the PPA and RSC, respectively.

Circ_0067934 reduces JNK phosphorylation through a microRNA-545-3p/PPA1 axis to enhance tumorigenesis and cisplatin resistance in ovarian cancer.

BACKGROUND: Circular RNA 0067934 (circ_0067934) has been revealed as a cancer driver in multiple human malignancies, whereas its action in the pathogenesis of ovarian cancer (OC) remains unclear. This study focuses on the function of circ_0067934 in tumorigenesis and cisplatin (DDP) resistance in OC and the molecular mechanism. METHODS: Expression of circ_0067934 in OC tissues and cells was examined, and its correlation with the clinical characteristics of patients was analyzed. Candidate targets of circ_0067934 were predicted using bioinformatics systems. Binding relationships between circ_0067934 and microRNA (miR)-545-3p and between miR-545-3p and inorganic pyrophosphatase 1 (PPA1) were validated via luciferase assays. Gain- and loss-of functions of circ_0067934, miR-545-3p and PPA1 were performed to determine their functions in proliferation, invasion, apoptosis and DDP resistance of OC cells in vitro and in vivo. RESULTS: Circ_0067934 was overexpressed in OC samples and associated with advanced tumor staging and lymph node metastasis. Downregulation of circ_0067934 reduced DDP resistance of the DDP-resistant A2780/DDP cell line and reduced cell proliferation and invasion, but the malignant behaviors of OC cells were restored after further miR-545-3p downregulation. Circ_0067934 served as a sponge for miR-545-3p and diminished its suppressive effect on PPA1 translation. Artificial upregulation of PPA1 enhanced proliferation, invasion and DDP resistance of A2780/DDP cells, and it reduced phosphorylation of the pro-apoptotic JNK signaling. Similar results were found in vivo. CONCLUSION: This study suggests that circ_0067934 sequesters miR-545-3p and enhances PPA1 expression to promote tumorigenesis and DDP resistance in OC. This study may provide novel approaches in the management of OC.

Plastid phylogenomic insights into relationships of all flowering plant families.

BACKGROUND: Flowering plants (angiosperms) are dominant components of global terrestrial ecosystems, but phylogenetic relationships at the familial level and above remain only partially resolved, greatly impeding our full understanding of their evolution and early diversification. The plastome, typically mapped as a circular genome, has been the most important molecular data source for plant phylogeny reconstruction for decades. RESULTS: Here, we assembled by far the largest plastid dataset of angiosperms, composed of 80 genes from 4792 plastomes of 4660 species in 2024 genera representing all currently recognized families. Our phylogenetic tree (PPA II) is essentially congruent with those of previous plastid phylogenomic analyses but generally provides greater clade support. In the PPA II tree, 75% of nodes at or above the ordinal level and 78% at or above the familial level were resolved with high bootstrap support (BP ≥ 90). We obtained strong support for many interordinal and interfamilial relationships that were poorly resolved previously within the core eudicots, such as Dilleniales, Saxifragales, and Vitales being resolved as successive sisters to the remaining rosids, and Santalales, Berberidopsidales, and Caryophyllales as successive sisters to the asterids. However, the placement of magnoliids, although resolved as sister to all other Mesangiospermae, is not well supported and disagrees with topologies inferred from nuclear data. Relationships among the five major clades of Mesangiospermae remain intractable despite increased sampling, probably due to an ancient rapid radiation. CONCLUSIONS: We provide the most comprehensive dataset of plastomes to date and a well-resolved phylogenetic tree, which together provide a strong foundation for future evolutionary studies of flowering plants.

Expression of Pinellia pedatisecta Agglutinin PPA Gene in Transgenic Sugarcane Led to Stomata Patterning Change and Resistance to Sugarcane Woolly Aphid, Ceratovacuna lanigera Zehntner.

The sugarcane woolly aphid is one of the main pests of sugarcane worldwide. The Pinellia pedatisecta agglutinin (PPA) gene has been demonstrated to function towards aphid resistance in other crops. In our study, in order to investigate the PPA function towards aphid control in sugarcane and its underlying mechanism, the PPA gene was overexpressed in a sugarcane Zhongzhe 1 (ZZ1) cultivar in independent transgenic sugarcane lines. It was confirmed in this study that PPA transgenic sugarcane can resist aphids via detecting the aphids' development and tracing the survival number on PPA-transgenic sugarcane lines as well as PPA negative control lines. The mechanism of PPA lectin-associated defense against aphids was preliminarily explored. Stomatal patterning differences of sugarcane leaves between PPA-transgenic sugarcane lines and negative control lines were found. PPA overexpression led to an increase in stomata number and a decrease in stomata size that might have changed the transpiration status, which is critical for aphids' passive feeding. Moreover, the antioxidant enzyme, sugar, tannin and chlorophyll content in sugarcane leaves before and after aphid infestation was determined. The results indicated that PPA overexpression in sugarcane resulted in an increase in antioxidant enzyme activity and tannin content, as well as a reduction in the decline of certain sugars. These together may improve sugarcane resistance against the sugarcane woolly aphid.

miRNA Expression Is Increased in Serum from Patients with Semantic Variant Primary Progressive Aphasia.

Primary progressive aphasia (PPA) damages the parts of the brain that control speech and language. There are three clinical PPA variants: nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). The pathophysiology underlying PPA variants is not fully understood, including the role of micro (mi)RNAs which were previously shown to play a role in several neurodegenerative diseases. Using a two-step analysis (array and validation through real-time PCR), we investigated the miRNA expression pattern in serum from 54 PPA patients and 18 controls. In the svPPA cohort, we observed a generalized upregulation of miRNAs with miR-106b-5p and miR-133a-3p reaching statistical significance (miR-106b-5p: 2.69 ± 0.89 mean ± SD vs. 1.18 ± 0.28, p < 0.0001; miR-133a-3p: 2.09 ± 0.10 vs. 0.74 ± 0.11 mean ± SD, p = 0.0002). Conversely, in lvPPA, the majority of miRNAs were downregulated. GO enrichment and KEGG pathway analyses revealed that target genes of both miRNAs are involved in pathways potentially relevant for the pathogenesis of neurodegenerative diseases. This is the first study that investigates the expression profile of circulating miRNAs in PPA variant patients. We identified a specific miRNA expression profile in svPPA that could differentiate this pathological condition from other PPA variants. Nevertheless, these preliminary results need to be confirmed in a larger independent cohort.

Restoration of Cathepsin D Level via L-Serine Attenuates PPA-Induced Lysosomal Dysfunction in Neuronal Cells.

L-serine is a non-essential amino acid endogenously produced by astrocytes and is abundant in human diets. Beneficial roles of the metabolic products from L-serine in various conditions in the brain including neuronal development have been reported. Through several preclinical studies, L-serine treatment was also shown to offer beneficial therapeutic effects for brain damage such as ischemic stroke, amyotrophic lateral sclerosis, and Parkinson's disease. Despite evidence for the value of L-serine in the clinic, however, its beneficial effects on the propionic acid (PPA)-induced neuronal toxicity and underlying mechanisms of L-serine-mediated neuroprotection are unknown. In this study, we observed that PPA-induced acidic stress induces abnormal lipid accumulation and functional defects in lysosomes of hippocampal neurons. L-serine treatment was able to rescue the structure and function of lysosomes in PPA-treated hippocampal neuronal cells. We further identified that L-serine suppressed the formation of lipid droplets and abnormal lipid membrane accumulations inside the lysosomes in PPA-treated hippocampal neuronal cells. Taken together, these findings indicate that L-serine can be utilized as a neuroprotective agent for the functionality of lysosomes through restoration of cathepsin D in disease conditions.