Center for Muscle Health and Neuromuscular Disorders

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder causing progressive muscle degeneration. Although cardiomyopathy is a leading mortality cause in DMD patients, the mechanisms underlying heart failure are not well understood. Previously, we showed that NF-κB exacerbates DMD skeletal muscle pathology by promoting inflammation and impairing new muscle growth. Here, we show that NF-κB is activated in murine dystrophic (mdx) hearts, and that cardiomyocyte ablation of NF-κB rescues cardiac function. This physiological improvement is associated with a signature of upregulated calcium genes, coinciding with global enrichment of permissive H3K27 acetylation chromatin marks and depletion of the transcriptional repressors CCCTC-binding factor, SIN3 transcription regulator family member A, and histone deacetylase 1. In this respect, in DMD hearts, NF-κB acts differently from its established role as a transcriptional activator, instead promoting global changes in the chromatin landscape to regulate calcium genes and cardiac function.

OBJECTIVE: Intestinal ischemia and reperfusion injury was known to cause postinjury multiple organ failure by neutrophil and unclear nonneutrophil factors. Peroxynitrite formed by the rapid reaction between superoxide and nitric oxide, is a toxic substance that contributes to tissue injury in a number of biological systems. In this study, the role of nitric oxide and neutrophils on lung damage after burn was investigated. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury models in the rat. INTERVENTIONS: In experiment 1, specific pathogen-free Sprague-Dawley rats underwent 35% total body surface area burn. At 4, 8, 16, and 24 hrs after burn, intestinal mucosa and lung tissue were harvested for myeloperoxidase (MPO) assay, blood was collected for measurement of peroxynitrite-mediated oxidation of dihydrorhodamine 123, and pulmonary microvascular dysfunction was quantified by measuring the extravasation of Evans blue dye. In experiment 2, polymorphonuclear granulocyte antibody (0.12 mL/100 g administered intraperitoneally 16 hrs before burn), S-methylisothiourea (7.5 mg/kg, intraperitoneally, immediately after burn), a specific inducible nitric oxide synthase inhibitor, and sterile saline (15 mL/kg, intraperitoneally, immediately after burn) were given to different groups of thermally injured animals individually. The plasma dihydrorhodamine 123 oxidation level, intestinal and lung MPO activity, lung permeability, and lung histology were evaluated at 8 hrs after burn. The cellular localization of nitrotyrosine, a marker for peroxynitrite reactivity, was also examined by immunostaining. In experiment 3, 3-morpholinosydnonimine (10 mM, intraperitoneally), a peroxynitrite donor, was given to nonburned rats to examine the peroxynitrite effect on lung inducible nitric oxide synthase expression. MEASUREMENTS AND MAIN RESULTS: The level of MPO activity in intestine and lung, blood dihydrorhodamine 123 oxidation, and lung permeability were increased up to 2-fold, 2.5-fold, 2-fold, and 2-fold of normal, respectively, at 8 hrs after burn. S-methylisothiourea injection significantly decreased (p <.05) 31% of the lung MPO activity, 41% of the blood peroxynitrite level, 54% of the lung permeability, and the lung peroxynitrite production in burned rats. Polymorphonuclear granulocyte antibody pretreatment significantly decreased 60% of the intestinal MPO, 92% of the blood peroxynitrite level, and 56% the lung MPO activity in burned rats, but the lung permeability was only slightly decreased by polymorphonuclear granulocyte antibody pretreatment. Furthermore, 3-morpholinosydnonimine increased the lung inducible nitric oxide synthase messenger RNA levels. CONCLUSIONS: Thermal injury induces blood dihydrorhodamine 123 oxidation, intestinal and lung neutrophil deposition, lung nitrotyrosine production, and lung damage. Both specific inhibition of inducible nitric oxide synthase and polymorphonuclear granulocyte antibody pretreatment decrease blood dihydrorhodamine 123 oxidation and intestinal and lung neutrophil deposition, but only inducible nitric oxide synthase inhibition with S-methylisothiourea reduces lung peroxynitrite production and thermal injury-induced lung damage. Nitric oxide and the ensuing peroxynitrite production in lung play a more important role than neutrophil in contributing to thermal injury-induced lung damage.

OBJECTIVE: The molecular mechanisms of lung damage following thermal injury are not clear. The purpose of this study was to determine whether interleukin (IL)-1 mediates burn-induced inducible nitric oxide synthase (iNOS) expression, peroxynitrite production, and lung damage through c-Jun NH2-terminal kinase (JNK) signaling. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury models in the mice. INTERVENTIONS: IL-1 receptor type 1 (IL-1R1) mice, Tnfrsf1a mice, and wild-type (WT) mice were subjected to 30% total body surface area third-degree burn. The JNK inhibitor, SP600125, was given to mice to study the involvement of the JNK pathway in thermal injury-induced lung damage. WT --> WT, WT --> IL-1R1, and IL-1R1 --> WT chimeric mice were generated to determine the role of hematopoietic cells in IL-1-mediated lung damage. Neutrophils were harvested and treated in vitro with N-formyl-methionyl-leucyl-phenylalanine (fMLP). MEASUREMENTS AND MAIN RESULTS: IL-1R1 mice rather than Tnfrsf1a mice showed less thermal injury-induced lung damage. IL-1R1 mice displayed less lung JNK activity; intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), chemokine receptor 2 (CXCR2), and macrophage inflammatory protein-2 (MIP2), messenger RNA expression; myeloperoxidase activity; and neutrophil p38 mitogen-activated protein kinase (MAPK) phosphorylation after thermal injury. SP600125 significantly reduced thermal injury-induced blood dihydrorhodamine (DHR) 123 oxidation, iNOS expression, and lung permeability in WT mice but not in IL-1R1 mice. IL-1R1 --> WT chimeric mice rather than WT --> IL-1R1 chimeric mice showed less thermal injury-induced lung damage. fMLP increased reactive oxygen species (ROS) production of neutrophils in WT mice but not in IL-1R1 mice. SP600125 decreased ROS production of neutrophils in WT mice but not in IL-1R1 mice. CONCLUSIONS: Thermal injury-induced lung JNK activation; lung ICAM, VCAM, CXCR2, and MIP2 expression; and DHR 123 oxidation are IL-1 dependent. JNK inhibition decreases IL-1-mediated thermal injury-induced lung damage. Given that the IL-1 receptor is critical in thermal injury-induced p38 MAPK phosphorylation and ROS production of neutrophils, we conclude that IL-1 mediates thermal injury-induced iNOS expression and lung damage through the JNK signaling pathway.

Abstract We identified ten persons in six consanguineous families with Distal Arthrogryposis (DA) who had congenital contractures, scoliosis, and short stature. Exome sequencing revealed that each affected person was homozygous for one of two different rare variants (c.470G&gt;T, p.(Cys157Phe) or c.469T&gt;C, p.(Cys157Arg)) affecting the same residue of myosin light chain, phosphorylatable, fast skeletal muscle ( MYLPF) . In a seventh family, a c.487G&gt;A, p.(Gly163Ser) variant in MYLPF arose de novo in a father, who transmitted it to his son. In an eighth family comprised of seven individuals with dominantly-inherited DA, a c.98C&gt;T, p.(Ala33Val) variant segregated in all four persons tested. Variants in MYLPF underlie both dominant and recessively inherited DA. Mylpf protein models suggest that the residues associated with dominant DA interact with myosin whereas the residues altered in families with recessive DA only indirectly impair this interaction. Pathological and histological exam of a foot amputated from an affected child revealed complete absence of skeletal muscle (i.e., segmental amyoplasia). To investigate the mechanism for this finding, we generated an animal model for partial MYLPF impairment by knocking out zebrafish mylpfa . The mylpfa mutant had reduced trunk contractile force and complete pectoral fin paralysis, demonstrating that mylpf impairment most severely affects limb movement. mylpfa mutant muscle weakness was most pronounced in an appendicular muscle and was explained by reduced myosin activity and fiber degeneration. Collectively, our findings demonstrate that partial loss of MYLPF function can lead to congenital contractures, likely as a result of degeneration of skeletal muscle in the distal limb.

# Taiwan Political-Military Events Dataset (2020-2025) ## Dataset Overview This dataset documents significant political and military events related to Taiwan from February 2020 to November 2025, including PLA military activities, U.S.-Taiwan interactions, political statements, and foreign naval vessel transits through the Taiwan Strait. **Dataset Information:** - **Time Period:** 2020-02-15 to 2025-11-25 - **Total Records:** 265 event records - **Language:** Bilingual (English translations + Chinese original) - **Geographic Focus:** Taiwan Strait region and cross-Strait relations - **Data Sources:** Taiwan Ministry of National Defense, media reports, official government statements ## File Description ### taiwan_political_military_events_dataverse.csv Main tabular data file containing chronological event records with bilingual content. **File Format:** CSV (UTF-8 encoding) **Dimensions:** 265 rows × 16 columns ## Variable Definitions | Column Name | Data Type | Description | |------------|-----------|-------------| | `date` | Date | Event date (YYYY-MM-DD format) | | `year` | Integer | Year | | `month` | Integer | Month (1-12) | | `day` | Integer | Day of month | | `year_month` | Text | Year-month code (e.g., "20-Feb") | | `weekday` | Text | English day of week | | `weekday_english` | Text | English day of week (duplicate for clarity) | | `pla_aircraft_sorties` | Integer | Number of PLA aircraft sorties around Taiwan | | `china_carrier_present` | Binary | Aircraft carrier presence (1=Yes, 0=No) | | `us_taiwan_interaction_en` | Text | U.S.-Taiwan interaction description (English) | | `us_taiwan_interaction_zh` | Text | U.S.-Taiwan interaction description (Chinese) | | `political_statement_en` | Text | Political statements description (English) | | `political_statement_zh` | Text | Political statements description (Chinese) | | `foreign_battleship_en` | Text | Foreign naval vessels description (English) | | `foreign_battleship_zh` | Text | Foreign naval vessels description (Chinese) | | `weekday_chinese` | Text | Chinese day of week (繁體中文) | ## Data Processing Notes ### Original Data Issues The original dataset had: 1. Numerous empty rows (2,193 out of 2,458 rows) 2. Mixed date formats 3. Chinese-only text content requiring translation ### Data Cleaning Steps 1. **Empty Row Removal:** Filtered out 2,193 rows with no date information 2. **Date Standardization:** Converted all dates to ISO 8601 format (YYYY-MM-DD) 3. **Column Renaming:** Standardized all column names to lowercase with underscores 4. **Bilingual Content:** Added English translations alongside Chinese original text 5. **Missing Values:** Numeric columns filled with 0, text columns with empty strings 6. **Encoding:** UTF-8 encoding throughout for international character support ## Data Summary Statistics - **Total Event Records:** 265 - **Date Range:** 2020-02-15 to 2025-11-25 - **Time Span:** Nearly 6 years ### Event Coverage - **Records with PLA Aircraft Sorties:** 151 (57.0%) - **Records with Carrier Present:** 78 (29.4%) - **U.S.-Taiwan Interactions:** 9 events - **Political Statements:** 35 records - **Foreign Naval Vessel Transits:** 12 records ### PLA Activity Summary - **Average Aircraft Sorties (when &gt;0):** Varies from 2 to several dozen - **Carrier Presence Days:** 78 days recorded - **Peak Activity Periods:** 2022-2024 (post-Pelosi visit) ## Event Categories ### 1. PLA Military Activities - Aircraft sorties entering Taiwan's ADIZ - Aircraft carrier operations - Large-scale military exercises - Live-fire drills ### 2. U.S.-Taiwan Interactions - High-level official visits (e.g., Pelosi, Azar) - Congressional delegations - Military cooperation announcements - Transit stops by Taiwan officials ### 3. Political Statements - **U.S. Statements:** Policy reaffirmations, commitments to Taiwan - **CCP Statements:** Protests, warnings, exercise announcements - **Taiwan Statements:** Responses to PRC pressure, gratitude for U.S. support ### 4. Foreign Naval Vessels - U.S. Navy transits (most frequent) - Canadian Navy passages - UK Royal Navy transits - Australian Navy operations - Japanese MSDF movements ## Usage Notes ### Bilingual Content Structure - All text fields have both `_en` (English) and `_zh` (Chinese) versions - Original Chinese preserved for verification and Chinese-language research - English translations suitable for international academic use ### Missing Values - Blank cells in binary indicator columns mean "No" or "Not recorded" - Empty strings in text columns indicate no event of that type occurred - Numeric columns use 0 for days with no recorded activity ### Recommended Analysis Approaches 1. **Time Series Analysis:** Track escalation patterns over time 2. **Event Correlation:** Examine relationships between U.S. actions and PRC responses 3. **Discourse Analysis:** Analyze political statement framing 4. **Crisis Dynamics:** Study action-reaction patterns during tensions 5. **Network Analysis:** Map relationships between actors and events ### Software Compatibility - **Python:** Use `pd.read_csv(encoding='utf-8')` - **R:** Use `read.csv(fileEncoding='UTF-8')` - **Stata:** Use `import delimited, encoding(UTF-8)` - **Excel:** Import via Power Query with UTF-8 encoding ## Key Events Captured ### Major Escalation Points - **August 2020:** U.S. HHS Secretary Azar visits Taiwan - **January 2021:** Taiwan representative invited to Biden inauguration - **August 2022:** House Speaker Pelosi visits Taiwan (major PLA exercises) - **April 2023:** President Tsai meets House Speaker McCarthy (3-day exercises) - **May 2024:** President Lai inaugural address (PLA response exercises) ### Persistent Patterns - Regular PLA aircraft incursions - U.S. Navy "freedom of navigation" transits - Allied naval presence (Canada, UK, Australia) - Tit-for-tat political statements ## Data Quality - **Completeness:** All dates covered; event fields have expected sparsity - **Accuracy:** Cross-referenced with official government sources and major media - **Timeliness:** Updated through November 2025 - **Translation Quality:** Professional translation maintaining accuracy and context ## Limitations 1. **Selection Bias:** Only includes publicized events; classified activities not captured 2. **Reporting Lag:** Some events may be reported days after occurrence 3. **Granularity:** Daily-level data; intraday timing not captured 4. **Scope:** Primarily military/political events; economic measures not included ## Citation If you use this dataset, please cite: ``` Taiwan Political-Military Events Dataset (2020-2025). [Dataset]. Available at: [Your Dataverse URL] ``` ## Related Datasets This dataset complements: - PLA Sorties Around Taiwan (2015-2026) - Taiwan Strait Crisis Event Database - Cross-Strait Relations Timeline ## Contact Information For questions about this dataset, please contact: [Your Contact Information] ## License [Specify your data license here, e.g., CC0, CC-BY 4.0, etc.] ## Version History - **Version 1.0** (2026-01-01): Initial release with bilingual content and comprehensive event coverage --- *Last Updated: 2026-01-01* *Prepared for Harvard Dataverse*