W chromosome sequences of two bombycid moths provide an insight into the origin of Fem.

Fem is a W-linked gene that encodes a piRNA precursor, and its product, Fem piRNA, is a master factor of female determination in Bombyx mori. Fem has low similarity to any known sequences, and the origin of Fem remains unclear. So far, two hypotheses have been proposed for the origin of Fem: The first hypothesis is that Fem is an allele of Masc, which assumes that the W chromosome was originally a homologous chromosome of the Z chromosome. The second hypothesis is that Fem arose by the transposition of Masc to the W chromosome. To explore the origin of Fem, we determined the W chromosome sequences of B. mori and, as a comparison, a closely relative bombycid species of Trilocha varians with a Fem-independent sex determination system. To our surprise, although the sequences of W and Z chromosomes show no homology to each other, a few pairs of homologues are shared by W and Z chromosomes, indicating the W chromosome of both species originated from Z chromosome. In addition, the W chromosome of T. varians lacks Fem, while the W chromosome of B. mori has over 100 copies of Fem. The high-quality assembly of the W chromosome of B. mori arose the third hypothesis about the origin of Fem: Fem is a chimeric sequence of multiple transposons. More than half of one transcriptional unit of Fem shows a significant homology to RTE-BovB. Moreover, the Fem piRNA-producing region could correspond to the boundary of the two transposons, gypsy and satellite DNA.

A tale of recurrent secretory carcinoma of submandibular gland in an adolescent male: A rare presentation of a rare tumor.

Mammary analogue secretory carcinoma (MASC) is a rare salivary gland tumor which shares its histologic, immunohistochemical, and genetic features with the secretory carcinoma (SC) of breast. In this case report, we describe a case of MASC in a young adolescent male with swelling in the right angle of mandible which is a relatively rare site to present along with its correlation of cytological, histological, and immunohistochemical features. A 16-year-old male came with the complaint of swelling in the right angle of mandible since 2 years. Contrast-enhanced computed tomography (CECT) neck revealed differential diagnosis of nerve sheath tumor, pleomorphic adenoma, and adenoid cystic neoplasm was kept, and subsequently fine-needle aspiration cytology (FNAC) was done. FNAC was done in which differential diagnosis of myoepithelial neoplasm, acinic cell carcinoma, and SC was given. Surgical excision was done followed by histopathological examination. Immunohistochemistry panel was also applied, and final diagnosis of SC was rendered. SC has distinct cytological, histological, and immunohistochemical features which should be recognized by the pathologists for the appropriate management of the patient.

Diagnostic Utility of Expression Pattern of S100/Mammaglobin/SOX10/DOG 1 Immunohistochemistry in Differentiation of Secretory and Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis.

Secretory carcinoma (SC) is a relatively new disease entity, separate from acinic cell carcinoma (AciCC), which frequently displays ETV6-NTRK3 gene fusion. However, the differences between SC and AciCC remain ambiguous. Genetic diversity makes its diagnosis complicated. In this regard combined expression of immunohistochemistry markers S100/Mammaglobin/SOX10 and DOG1 is need of the hour as alternative methodology. The current systematic review was to investigate the diagnostic utility of combined immunohistochemical expression of S100/Mammaglobin/SOX10/DOG1 in distinction of SC from AciCC histologically. An electronic search of databases was carried out using MEDLINE by PubMed, Google scholar, Scopus and Web of science. Articles inclusive of SC and AciCC were assessed with S100/Mammaglobin/SOX10/DOG1 immunohistochemistry and their predominant expression pattern, predictive values, sensitivity and specificity were gathered. Fourteen eligible articles were analysed, which revealed predominant immunostaining pattern of S100 + /Mammaglobin + /SOX10 + /DOG1- by nearly all ETV6::NTRK3 fusion prevalent SCs alongside with other gene fusions like RET, MET and MAML3 with 98.4% sensitivity as well as 86.1% specificity. The evidence supports that S100/Mammaglobin/SOX10/DOG1 combined immunostaining can serve as a reliable diagnostic method to differentiate secretory from acinic cell carcinoma.

Discrepancy of social cognition between bipolar disorders and major depressive disorders.

BACKGROUND: The research landscape examining social cognition (SC) impairment in patients with major depressive disorders (MDD) and bipolar disorders (BD) is notably scarce. Presently, assessments predominantly rely on static stimuli and self-reported measures, which may not capture the dynamic dimensions of social cognition. OBJECTIVES: This study aimed to validate the Chinese version of Movie Assessment of Social Cognition (MASC-CH) and to investigate whether MDD and BD exhibit distinct patterns of SC impairments, shedding light on potential differences between these two mood disorders. METHODS: The study encompassed 197 participants, aged 18-65, distributed as follows: 21 BD, 20 MDD, and 156 healthy controls (HC). We focused on examining "cognitive" and "emotional" SC scores and "undermentalizing" and "overmentalizing" error patterns, with nonsocial inference as a control. Additional assessments included the Reading Mind in the Eyes Test (RMET) and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). We also explored the association between depression severity (measured by the Hamilton Depressive Rating Scale, HDRS) and distinct SC dimensions between MDD and BD. RESULTS: The MASC-CH exhibited strong validity and reliability for SC assessment. In group comparisons, BD participants scored significantly lower on MASC-CH, while the MDD group scores were not significantly different from HC. Specifically, BD individuals had notably lower cognitive SC scores and made more undermentalizing and absence of mentalizing errors than MDD and HC. Additionally, a negative correlation between HDRS score and overmentalizing was observed in BD, not in the MDD. CONCLUSIONS: The findings indicate that depression severity scores in BD were inversely related to MASC-CH scores. In contrast, this relationship was not observed in the MDD group. These results underscore the importance of SC impairments as distinguishing characteristics of both BD and MDD. It provides valuable insights into the distinct social-cognitive profiles of both mood disorders.

Social cognition in women with borderline personality disorder based on an exhaustive analysis of the Movie for Assessment of Social Cognition (MASC) categories.

A significant number of borderline personality disorder (BPD) symptoms are manifested in the interpersonal context. This can be explained by the difficulties in attributing the mental states of oneself and others, which constitutes social cognition. Errors in social cognition are interrelated with the affective, cognitive, impulsive, and interpersonal areas of the person with BPD. The aims of this study was to analyze social cognition in women with BPD compared with a control group and to analyze social cognition in BPD based on BPD symptoms and its severity. To assess social cognition, we used a full range of social cognition categories provided by the Movie for the Assessment of Social Cognition (MASC): correct theory of mind (ToM); attribution of mental states (thoughts, emotions, or intentions); errors of mentalization; types of ToM; and attribution of mental states through perceptive or cognitive cues and through hot or cold emotions. The MASC has high ecological validity and has been validated in Spanish. The sample comprised 79 women, including 47 women with BPD and 32 healthy women. Worse social cognition performance was observed in women with BPD. More severe borderline symptoms were related to worse functioning in the correct ToM and to errors of no mentalization. Involvement of the cognitive area in borderline symptoms was associated with worse functioning in correct ToM and worse social cognition in cognitive areas as well as with hypermentalization. This is the first study that uses all the MASC categories and considers BPD heterogeneity and its severity to study social cognition.

Effects of age on behavioural and eye gaze on Theory of Mind using movie for social cognition.

Evidence has shown that older adults have lower accuracy in Theory of Mind (ToM) tasks compared with young adults, but we are still unclear whether the difficulty in decoding mental states in older adults stems from not looking at the critical areas, and more so from the ageing Asian population. Most ToM studies use static images or short vignettes to measure ToM but these stimuli are dissimilar to everyday social interactions. We investigated this question using a dynamic task that measured both accuracy and error types, and examined the links between accuracy and error types to eye gaze fixation at critical areas (e.g., eyes, mouth, body). A total of 82 participants (38 older, 44 young adults) completed the Movie for the Assessment of Social Cognition (MASC) task on the eye tracker. Results showed that older adults had a lower overall accuracy with more errors in the ipo-ToM (under-mentalising) and no-ToM (lack of mentalisation) conditions compared with young adults. We analysed the eye gaze data using principal components analysis and found that increasing age and looking less at the face were related to lower MASC accuracy in our participants. Our findings suggest that ageing deficits in ToM are linked to a visual attention deficit specific to the perception of socially relevant nonverbal cues.

Masculinizer gene controls sexual differentiation in Hyphantria cunea.

The Masculinizer gene, Masc, encodes a lepidopteran-specific novel CCCH-type zinc finger protein, which controls sex determination and dosage compensation in Bombyx mori. Considering the potential application of it in pest control, it is necessary to investigate the function of Masc gene in Hyphantria cunea, a globally invasive forest pest. In the present study, we identified and functionally characterized the Masc gene, HcMasc, in H. cunea. Sequence analysis revealed that HcMASC contained the conserved CCCH-type zinc finger domain, nuclear localization signal, and male determining domain, in which the last was confirmed to be required for its masculinization in BmN cell line. However, expression data showed that unlike male-biased expression in B. mori, HcMasc gene expresses in main all developmental stages or tissues in both sexes. Clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR-associated protein 9-based disruption of the common exons 1 and 3 of the HcMasc gene resulted in imbalanced sex ratio and abnormal external genitalia of both sexes. Our results suggest that the HcMasc gene is required for both male and female sexual differentiation and dosage compensation in H. cunea and provide a foundation for developing better strategies to control this pest.

Niche inflammatory signals control oscillating mammary regeneration and protect stem cells from cytotoxic stress.

Stem cells are known for their resilience and enhanced activity post-stress. The mammary gland undergoes frequent remodeling and is subjected to recurring stress during the estrus cycle, but it remains unclear how mammary stem cells (MaSCs) respond to the stress and contribute to regeneration. We discovered that cytotoxic stress-induced activation of CD11c+ ductal macrophages aids stem cell survival and prevents differentiation. These macrophages boost Procr+ MaSC activity through IL1ß-IL1R1-NF-κB signaling during the estrus cycle in an oscillating manner. Deleting IL1R1 in MaSCs results in stem cell loss and skewed luminal differentiation. Moreover, under cytotoxic stress from the chemotherapy agent paclitaxel, ductal macrophages secrete higher IL1ß levels, promoting MaSC survival and preventing differentiation. Inhibiting IL1R1 sensitizes MaSCs to paclitaxel. Our findings reveal a recurring inflammatory process that regulates regeneration, providing insights into stress-induced inflammation and its impact on stem cell survival, potentially affecting cancer therapy efficacy.

Mentalizing ability, mentalizing impairments, and anorexia nervosa: Validation of the Hebrew version of the Movie for the Assessment of Social Cognition (MASC).

The goal of this study was to validate the Hebrew version of the Movie for the Assessment of Social Cognition (MASC)-an ecological measure for assessing mentalizing ability-among patients with anorexia nervosa (AN) and healthy individuals. We examined the validity of the MASC's general mentalizing ability scale and of its mentalizing impairments subscales using validated measures of mentalizing ability (Reading the Mind in the Eyes test, Cambridge Mindreading Face-Voice Battery, and Reflective Function questionnaire) among female patients with AN (N = 35) and control participants (N = 42). ED symptoms were assessed via self-report questionnaires. The MASCHeb correlated with measures of mentalizing ability and was found to significantly differentiate patients with AN from controls. In addition to differing on general mental ability, the groups differed on hypomentalizing (but not hypermentalizing). Based on our findings, the MASCHeb proved to be an ecologically valid tool for assessing mentalizing ability and impairments among patients with AN. Moreover, our findings demonstrated the role played by general mentalizing ability in EDs and specifically pointed to the importance of hypomentalization in EDs. These findings have therapeutic implications, as outlined in the Discussion section.

A Parotid Gland Mammary Analogue Secretory Carcinoma in a 4-Year-Old Boy: Case Report and Literature Review.

Background: Mammary analogue secretory carcinoma (MASC) is characterized by similar histologic, immunohistochemical, and molecular features with breast secretory carcinoma. MASC usually occurs in adults. Case report: A 4-year-old boy presented with a right infra-auricular mass. Features of the tumor include solid, tubular, and papillary growth patterns, with homogenous eosinophilic secretions inside microcystic structures. Immunohistochemical stains showed strong, diffuse staining for CK7, S100, pan-TRK protein. P63 was positive in a peripheral pattern. Fluorescence in situ hybridization (FISH) analysis showed the characteristic ETV6-NTRK3 gene fusion. Conclusion: Typical histological, immunohistochemical, and molecular features are present in MASC occurring early in childhood.

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Current studies on water conservation capacity of litter in the mountainous area of Southwest China (MASC) mainly focus on local scale. Such results are difficult to evaluate the storage and water-holding capacity of litter in the whole MASC. In this study, the results of site-scale research in the MASC from 2004 to 2021 were collated (a total of 16 research sites and 70 data), as well as the storage and water-holding characteristics of litters of three typical forests in the MASC were compared and analyzed. The results showed that the water-holding processes of litter in coniferous forest, broadleaved forest and mixed forest were similar, which could be divided into three stages: rapid water absorption, gradual slowing, and stable. The absorption rate and duration of different forests were different in each stage. The broadleaved forest had the fastest water absorption rate, while coniferous forest had the slowest with the longest duration to reach stability. There was no significant difference in litter storage among diffe-rent forest types. The total litter storage of coniferous forest, broadleaved forest and mixed forest ranged from 8.26 to 8.82 t·hm-2. The significant spatial variations of litter storage in semi-decomposed layer resulted in that of total litter storage. The total maximum water-holding capacity of litters of the three forests ranged from 17.85 t·hm-2 to 19.87 t·hm-2, and the maximum water-holding rate of litter ranged from 200.6% to 228.0%. There was a positive correlation between the maximum water-holding capacity and litter storage in different forests. The total effective retention capacity of three forest litters ranged from 11.66 to 12.29 t·hm-2, while the total effective retention rate of three forests ranged from 128.1% to 145.2%. There were no significant differences in litter storage and water holding capacity among three forest types with two decomposition degrees in MASC.

Affective Empathy, Theory of Mind and Social Functioning in Patients With Focal Epilepsy.

Objective: Social cognition comprises basic and more complex functions, such as theory of mind (ToM) and affective empathy. Although everyday social interactions may be impaired if such higher-order social cognitive functions are compromised, associations between social functioning and social cognition in people with focal epilepsy (PWFE) are still poorly understood. We used a novel, naturalistic approach to investigate ToM in PWFE by applying the Movie for the Assessment of Social Cognition (MASC). Furthermore, we studied affective empathy, the relationship between social cognitive parameters and measures of social functioning, as well as between epilepsy focus and ToM. Methods: Thirty patients with either temporal (TLE) or frontal lobe epilepsy (FLE) were compared to 29 healthy control subjects (HC). In addition to the MASC, we applied questionnaire measures assessing empathy and everyday social functioning. Results: PWFE, especially with FLE, performed significantly worse than HC on the MASC. Perceived social integration and social activities, but not affective empathy, were reduced in PWFE. Regression analyses revealed associations between perceived social integration, clinical group status, affective empathy and ToM. Conclusion: PWFE displayed ToM deficits during a naturalistic task, whereas affective empathy was unimpaired. FLE may be associated with especially compromised ToM performance. Social cognition and social functioning appear to be interrelated in PWFE, whose self-perceived levels of social integration and social activities are lower than those of HC. More research into the association between social cognition and social functioning in PWFE is needed, in order to develop tailored intervention programs for these patients.

Transcriptome analysis in the silkworm Bombyx mori overexpressing piRNA-resistant Masculinizer gene.

Dosage compensation is a process that produces a similar expression of sex-linked and autosomal genes. In the silkworm Bombyx mori with a WZ sex-determination system, the expression from the single Z in WZ females matches that of ZZ males due to the suppression of Z-linked genes in males. A primary maleness determinant gene, Masculinizer (Masc), is also required for dosage compensation. In females, silkworm Piwi is complexed with the W chromosome-derived female-specific Feminizer (Fem) PIWI-interacting RNA (piRNA) and cleaves Masc mRNA. When Fem piRNA-resistant Masc cDNA (Masc-R) is overexpressed in both sexes, only female larvae are dead during the larval stage. In this study, transcriptome analysis was performed in neonate larvae to examine the effects of Masc-R overexpression on a global gene expression profile. Z-linked genes were globally repressed in Masc-R-overexpressing females due to force-driven dosage compensation. In contrast, Masc-R overexpression had little effect on the expression of Z-linked genes and the male-specific isoform of B. mori insulin-like growth factor II mRNA-binding protein in males, indicating that excessive Masc expression strengthens neither dosage compensation nor maleness in males. Fourteen genes were differentially expressed between Masc-R-overexpressing and control neonate larvae in both sexes, suggesting Masc functions other than dosage compensation and masculinization.

A rapid reduction in tumor size by cyclin-dependent kinase inhibition in hormone receptor-positive postpartum breast cancer: a case report of two patients and a review of the literature.

Background: Postpartum breast cancer (PPBC) as an independent entity different from PABC. PPBC is defined as breast cancer (BC) diagnosed within 5 years after delivery in many relevant literatures and is associated with a poor prognosis and a decrease in overall survival. PPBC patients commonly present with inflammatory breast cancer (IBC) phenotype, multifocal lesions, and lymph node metastasis. Hormone receptor-positive (HR+) PPBC is an under-investigated subtype. In PPBC, the risk of death of HR+ subtype significantly increased two-fold, while that was only modestly increased for triple-negative breast cancer (TNBC) subtype, and was not significant in human epidermal growth factor receptor 2-positive (HER2+) subtype. HR+ PPBC is a subtype associating with enhanced signatures of cell cycle control, T-cell activation and exhaustion, decreased HR signaling, and altered P53 signaling. The recommended treatment for HR+ PPBC patients is still lacking. Cyclin-dependent kinase (CDK) 4/6 inhibitors are used as a novel treatment standard not only in pretreated patients but also in the first-line setting of HR+ metastatic breast cancer (MBC). However, there is no clinical case report on the application and efficacy of CDK4/6 inhibitors in HR+ PPBC patients. Case Description: This article describes the clinical cases of two patients with advanced HR+ PPBC who were rapidly relieved after receiving leuprorelin combined with letrozole combined with dalpiciclib. We reviewed the related literature of PPBC, and found that HR+ PPBC has not been clinically classified as a BC subtype, and only some basic studies suggested that HR+ PPBC may be sensitive to CDK4/6 inhibitors. The purpose of this study is to provide the basis for the related research on the therapeutic effect of CDK4/6 inhibitors in HR+ PPBC through the report of clinical cases. Conclusions: This article reports for the first time the good therapeutic effects of CDK4/6 inhibitors on HR+ PPBC patients. Based on our findings, we suggest that dalpiciclib combined with endocrine therapy can be considered as the first-line treatment for patients with advanced HR+ PPBC. Our case report provides new clinical evidence for the related research on the role of CDK4/6 inhibitors in HR+ PPBC therapy.

A dual-luciferase reporter system for characterization of small RNA target genes in both mammalian and insect cells.

MicroRNAs (miRNAs) are regulatory RNA molecules that bind to target messenger RNAs (mRNAs) and affect the stability or translational efficiency of the bound mRNAs. Single or dual-luciferase reporter systems have been successfully used to identify miRNA target genes in mammalian cells. These reporter systems, however, are not sensitive enough to verify miRNA-target gene relationships in insect cell lines because the promoters of the target luciferase (usually Renilla) used in these reporter systems are too weak to drive sufficient expression of the target luciferase in insect cells. In this study, we replaced the SV40 promoter in the psiCHECK-2 reporter vector, which is widely used with mammalian cell lines, with the HSV-TK or AC5.1 promoter to yield two new dual-luciferase reporter vectors, designated psiCHECK-2-TK and psiCHECK-2-AC5.1, respectively. Only psiCHECK-2 and psiCHECK-2-AC5.1 had suitable target (Renilla)/reference (firefly) luciferase activity ratios in mammalian (HeLa and HEK293) and insect (Sf9, S2, Helicoverpa zea fat body and ovary) cell lines, while psiCHECK-2-TK had suitable Renilla/firefly luciferase activity ratios regardless of the cell line. Moreover, psiCHECK-2-TK successfully detected the interaction between Helicoverpa armigera miRNA9a and its target, the 3'-untranslated region of heat shock protein 90, in both mammalian and H. zea cell lines, but psiCHECK-2 failed to do so in H. zea cell lines. Furthermore, psiCHECK-2-TK with the target sequence, HzMasc (H. zea Masculinizer), accurately differentiated between H. zea cell lines with or without the negative regulation factor (miRNA or piRNA) of HzMasc. These data demonstrate that psiCHECK-2-TK can be used to functionally characterize small RNA target genes in both mammalian and insect cells.

Mammary analogue secretory carcinoma: A challenging case arising in a young man with radiation exposure.

Mammary Analogue Secretory Carcinoma (MASC) is a recently described salivary gland tumor frequently sampled via fine-needle aspiration. The cytologic features of MASC are not entirely distinctive and can simulate acinic cell carcinoma, but the tumor harbors an ETV6 gene rearrangement resulting in an ETV6-NTRK3 fusion gene. We present a case of MASC arising in a 31 year old man with a history of multiple radio-embolization procedures.

Cytomorphological features of Mammary Analog secretory carcinoma of parotid gland: Report of 3 cases and review of literature.

Mammary analog secretory carcinoma (MASC) of salivary gland is a recently described entity. Due to its rarity and cytomorphological overlap with other salivary gland tumors, it is often difficult to recognize on cytology. Here we describe three such cases with their histopathological correlation. All the three tumors arose in the parotid gland. They were misdiagnosed as mucoepidermoid carcinoma, acinic cell carcinoma and salivary duct adenocarcinoma, respectively. Final diagnosis of MASC was established on their follow-up histopathology and immunochemistry evaluation. Cytosmears of these tumors showed high cellularity with papillary architecture lying within fluid background rich in foamy macrophages. Nuclear atypia varied from minimal to marked with frequent mitosis and presence of necrosis. Cytoplasmic vacuolation was a consistent finding. Although the cytomorphological features of MASC are not specific, a diagnosis of MASC should be strongly considered in the presence of papillary architecture, prominent cytoplasmic vacuolations of the tumor cells and a background of cyst fluid. Immunohistochemistry on cell block may be done to confirm the diagnosis.

Mind reading improvements in mentalization-based therapy training.

The psychological strain of many psychiatric disorders arises from difficulties encountered in social interactions. Social withdrawal is often the first symptom of neuropsychiatric disorders. The authors explore the various options for training social cognition skills. Social cognition was assessed using the Movie for the Assessment of Social Cognition (MASC). After completion of mentalization-based therapy (MBT) training, MASC scores improved significantly in health care providers (p = .006, r = .57). Mentalizing (operationalized with reflective functioning [RF]) was assessed in the MBT group (Group A) and compared with RF in a control group (Group B). RF was significantly higher in Group A (RF = 4.35, SD = 1.19) than in Group B (RF = 3.43, SD = 1.70) (p = .0385; Cohen's d = 0.65). MBT might be a promising intervention in social cognition training. Mentalizing skills might be associated with attitude.

Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers.

Tropomyosin receptor kinase A, B and C (TRKA, TRKB and TRKC), which are well-known members of the cell surface receptor tyrosine kinase (RTK) family, are encoded by the neurotrophic receptor tyrosine kinase 1, 2 and 3 (NTRK1, NTRK2 and NTRK3) genes, respectively. TRKs can regulate cell proliferation, differentiation and even apoptosis through the RAS/MAPKs, PI3K/AKT and PLCγ pathways. Gene fusions involving NTRK act as oncogenic drivers of a broad diversity of adult and pediatric tumors, and TRKs have become promising antitumor targets. Therefore, achieving a comprehensive understanding of TRKs and relevant TRK inhibitors should be urgently pursued for the further development of novel TRK inhibitors for potential clinical applications. This review focuses on summarizing the biological functions of TRKs and NTRK fusion proteins, the development of small-molecule TRK inhibitors with different chemotypes and their activity and selectivity, and the potential therapeutic applications of these inhibitors for future cancer drug discovery efforts.