Interleukin 4 improved adipose-derived stem cells engraftment via interacting with fibro/adipogenic progenitors in dystrophic mice.

Adipose-derived stem cells (ADSC) therapy shows promise as an effective treatment for dystrophinopathy. Fibro-/adipogenic progenitors (FAPs) play an essential role in the myogenesis of muscle satellite cells and contribute to muscle fibrosis and adipocyte infiltration. The interleukin 4 (IL-4) pathway acts as a switch that regulates the functions of FAPs. The interaction between FAPs and engrafted cells remains unclear. In this study, we used a co-culture system to investigate possible crosstalk between the FAPs of dystrophic mice and ADSC overexpressing IL4 (IL4-ADSC) and control ADSC. Systemic transplantation of IL4-ADSC and control ADSC in dystrophic mice was conducted for 16 weeks, after which motor function and molecular improvements were evaluated. Overexpression of IL4 in ADSC significantly promoted myogenesis in vitro, increasing the expression of Pax7, Myogenin, and MyHC. Co-culture indicated that although myoblasts derived from control ADSC promoted adipogenic and fibrogenic differentiation of FAPs, FAPs did not significantly affect myogenesis of ADSC-derived myoblasts. However, overexpression of IL4 in ADSC inhibited their myotube-dependent promotion of FAPs differentiation on the one hand and promoted FAPs to enhance myogenesis on the other. Dystrophic mice administered with IL4-ADSC-derived myoblasts displayed significantly better motor ability, more engrafted cells showing dystrophin expression, and less muscle fibrosis, intramuscular adipocytes, and macrophage infiltration than mice administered control-ADSC-derived myoblasts. In conclusion, IL4 activation enhanced the therapeutic potential of ADSC transplantation in dystrophic mice, possibly by improving the myogenesis of IL4-ADSC and altering the crosstalk between engrafted stem cells and resident FAPs.

Research on electronic synaptic simulation of HfO2-based memristor by embedding Al2O3.

The potential of neuromorphic computing in synaptic simulation has led to a renewed interest in memristor. However, the demand for multilevel resistive switching with high reliability and low power consumption is still a great resistance in this application. In this work, the electronic synaptic plasticity and simulated bipolar switching behavior of Pt/Al2O3(2 nm)/HfO2(10 nm)/Al2O3(2 nm)/Ti tri-layer memristor is investigated. The effect of Al2O3layer embedded at the top electrode and the bottom electrode on the resistive performance of the memristor was studied. It is found that both of them can effectively improve the reliability of the device (104cycles), the resistive window (>103), the tunable synaptic linearity and reduce of the operating voltage. RRAM with Al2O3embedded at the top electrode have higher uniformity and LTP linearity, while those with Al2O3embedded at the bottom electrode significantly reduce the operating current (∼10µA) and improve LTD linearity. Electron transport mechanisms were compared between single-layer HfO2and tri-layer Al2O3/HfO2/Al2O3samples under DC scanning. The results showed that the thin Al2O3layer at the top electrode led to Fowler Northeim tunneling in the low-resistance state, while the thin Al2O3layer at the bottom electrode led to Schottky emission in the high-resistance state. The Al2O3/HfO2/Al2O3memristors were successfully used to achieve synaptic properties, including enhancement, inhibition, and spike time-dependent plasticity, demonstrating an important role in high-performance neuromorphic computing applications.

Serum creatinine as a biomarker for dystrophinopathy: a cross-sectional and longitudinal study.

BACKGROUND: Dystrophinopathy, a common neuromuscular disorder, includes Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Many researches are currently ongoing to develop curative approaches, which results in an urgent need for biomarkers of disease progression and treatment response. This study investigated whether the serum creatinine (SCRN) level can be used as a biomarker of disease progression in dystrophinopathy. METHODS: We enrolled 377 male patients with dystrophinopathy and 520 male non-dystrophinopathy controls in a cross-sectional study. From this cohort, 113 follow-up patients were enrolled in a longitudinal study. Patients' demographic information, motor function, muscle fatty infiltration, and muscle dystrophin levels were evaluated. We investigated correlations between these parameters and SCRN levels, and determined changes in SCRN levels with maturation and with motor function changes. RESULTS: Our results showed SCRN levels correlated with motor function (FDR < 0.001) and timed test results (FDR between < 0.001-0.012), as well as with muscle fatty infiltration (FDR < 0.001) and dystrophin levels (FDR = 0.015 and 0.001). SCRN levels increased with maturation in control individuals; it slowly increased with maturation in patients with BMD but decreased generally with maturation in patients with DMD. The longitudinal study further demonstrated that SCRN levels were associated with motor function. CONCLUSIONS: These findings indicated that the SCRN level is a promising biomarker for assessing disease progression in dystrophinopathy and could be used as a potential outcome measure in clinical trials.

Multiple-Molecule Drug Design Based on Systems Biology Approaches and Deep Neural Network to Mitigate Human Skin Aging.

Human skin aging is affected by various biological signaling pathways, microenvironment factors and epigenetic regulations. With the increasing demand for cosmetics and pharmaceuticals to prevent or reverse skin aging year by year, designing multiple-molecule drugs for mitigating skin aging is indispensable. In this study, we developed strategies for systems medicine design based on systems biology methods and deep neural networks. We constructed the candidate genomewide genetic and epigenetic network (GWGEN) via big database mining. After doing systems modeling and applying system identification, system order detection and principle network projection methods with real time-profile microarray data, we could obtain core signaling pathways and identify essential biomarkers based on the skin aging molecular progression mechanisms. Afterwards, we trained a deep neural network of drug-target interaction in advance and applied it to predict the potential candidate drugs based on our identified biomarkers. To narrow down the candidate drugs, we designed two filters considering drug regulation ability and drug sensitivity. With the proposed systems medicine design procedure, we not only shed the light on the skin aging molecular progression mechanisms but also suggested two multiple-molecule drugs for mitigating human skin aging from young adulthood to middle age and middle age to old age, respectively.

Non-Maternal Infant Handling in Wild Formosan Macaques of Mount Longevity, Taiwan.

In this paper, we present quantitative data on how the social network and sex of infants influence allomothering behaviour among wild Formosan macaques, Macaca cyclopis. Using long-term field data collected from the Mount Longevity study site in Kaohsiung (Taiwan), we have tested relevant hypotheses incorporating data on age, rank and reproductive state of infant handlers, and the relationship between handlers and infants. The results support 2 major hypotheses, i.e. those of reciprocity and alliance formation. Nevertheless, neither could account for the observed occurrences of unrelated infant handling by dominant females.

Biomechanical comparison of three stand-alone lumbar cages--a three-dimensional finite element analysis.

BACKGROUND: For anterior lumbar interbody fusion (ALIF), stand-alone cages can be supplemented with vertebral plate, locking screws, or threaded cylinder to avoid the use of posterior fixation. Intuitively, the plate, screw, and cylinder aim to be embedded into the vertebral bodies to effectively immobilize the cage itself. The kinematic and mechanical effects of these integrated components on the lumbar construct have not been extensively studied. A nonlinearly lumbar finite-element model was developed and validated to investigate the biomechanical differences between three stand-alone (Latero, SynFix, and Stabilis) and SynCage-Open plus transpedicular fixation. All four cages were instrumented at the L3-4 level. METHODS: The lumbar models were subjected to the follower load along the lumbar column and the moment at the lumbar top to produce flexion (FL), extension (EX), left/right lateral bending (LLB, RLB), and left/right axial rotation (LAR, RAR). A 10 Nm moment was applied to obtain the six physiological motions in all models. The comparison indices included disc range of motion (ROM), facet contact force, and stresses of the annulus and implants. RESULTS: At the surgical level, the SynCage-open model supplemented with transpedicular fixation decreased ROM (>76%) greatly; while the SynFix model decreased ROM 56-72%, the Latero model decreased ROM 36-91%, in all motions as compared with the INT model. However, the Stabilis model decreased ROM slightly in extension (11%), lateral bending (21%), and axial rotation (34%). At the adjacent levels, there were no obvious differences in ROM and annulus stress among all instrumented models. CONCLUSIONS: ALIF instrumentation with the Latero or SynFix cage provides an acceptable stability for clinical use without the requirement of additional posterior fixation. However, the Stabilis cage is not favored in extension and lateral bending because of insufficient stabilization.

Modeling and Simulation Investigation of Ferroelectric-Based Electrostatic Doping for Tunnelling Field-Effect Transistor.

In this paper, a novel ferroelectric-based electrostatic doping (Fe-ED) nanosheet tunneling field-effect transistor (TFET) is proposed and analyzed using technology computer-aided design (TCAD) Sentaurus simulation software. By inserting a ferroelectric film into the polarity gate, the electrons and holes are induced in an intrinsic silicon film to create the p-source and the n-drain regions, respectively. Device performance is largely independent of the chemical doping profile, potentially freeing it from issues related to abrupt junctions, dopant variability, and solid solubility. An improved ON-state current and ION/IOFF ratio have been demonstrated in a 3D-calibrated simulation, and the Fe-ED NSTFET's on-state current has increased significantly. According to our study, Fe-ED can be used in versatile reconfigurable nanoscale transistors as well as highly integrated circuits as an effective doping strategy.

The Image Identification Application with HfO2-Based Replaceable 1T1R Neural Networks.

This paper mainly studies the hardware implementation of a fully connected neural network based on the 1T1R (one-transistor-one-resistor) array and its application in handwritten digital image recognition. The 1T1R arrays are prepared by connecting the memristor and nMOSFET in series, and a single-layer and a double-layer fully connected neural network are established. The recognition accuracy of 8 × 8 handwritten digital images reaches 95.19%. By randomly replacing the devices with failed devices, it is found that the stuck-off devices have little effect on the accuracy of the network, but the stuck-on devices will cause a sharp reduction of accuracy. By using the measured conductivity adjustment range and precision data of the memristor, the relationship between the recognition accuracy of the network and the number of hidden neurons is simulated. The simulation results match the experimental results. Compared with the neural network based on the precision of 32-bit floating point, the difference is lower than 1%.

Comparison of Carrier and de novo Pathogenic Variants in a Chinese DMD/BMD Cohort.

Background: Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the DMD gene. With advances in prenatal diagnosis decreasing the number of affected offspring from carrier mothers, the frequency of de novo variants could increase. Therefore, determining the differences between the carrier and de novo variants of the DMD gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future. Methods: A total of 440 patients, 349 of whom had DMD and 91 had BMD, diagnosed in our department between 2012 and 2019, along with their respective mothers, were included in this study. Multiplex ligation-dependent probe amplification was used to detected deletions and duplications in patients and their mothers. Small mutations were detected using next-generation sequencing in the patients, followed by Sanger sequencing in the mothers. Results: Deletions, duplications, and small mutations were identified in 204, 46, and 99 of the 349 patients with DMD and in 50, 10, and 31 of the 91 patients with BMD, respectively. De novo deletions were more concentrated in hotspot regions than carrier deletions of DMD/BMD. No clear bias was observed in the variant distribution between carriers, de novo duplications, and small mutations in DMD/BMD. The carrier frequency of DMD (61.6%) was lower than that of BMD (69.2%), but the difference was not statistically significant. The carrier frequency of deletions of the DMD gene (51.2%) was significantly lower than those of duplications (75%) and small mutations (81.5%). Conclusion: Compared to de novo deletions, deletions from carrier mothers had a wider distribution. Moreover, there was no significant difference between the carrier frequencies of DMD and BMD. Duplications and small mutations were more commonly inherited, while deletions were present de novo.

A rare case of monozygotic triplets with Duchenne muscular dystrophy.

Twins with Duchenne muscular dystrophy (DMD) have been widely studied. We report the first rare case of monozygotic triplets with DMD who shared consistent phenotypes, including delayed motor and language milestones, muscle wasting and weakness, joint contracture, and lumbar lordosis. Muscle magnetic resonance imaging and biopsy revealed the similar muscle injury characteristics and dystrophin absence. Short tandem repeat analysis confirmed monozygosity. A de novo mutation (exon 49-52 deletion) was found in the triplets but not in their mother. Treatment included prednisone, idebenone, and rehabilitation management. At the 2-year follow-up, motor function had deteriorated, and muscle fatty infiltration was more extensive and severe. Our case offers a unique opportunity for genetic and therapeutic research. Furthermore, it highlights the critical role of genetic factors in DMD phenotypes and provides a potential choice for treatment observations.

Generation and characterization of an induced pluripotent stem cell line (ZSYYDNi001-A) from a patient with Duchenne muscular dystrophy carrying exon 51 deletion in the DMD gene.

Duchenne muscular dystrophy (DMD) is a common hereditary neuromuscular disease characterized by progressive muscle wasting and weakness. DMD is caused by mutations in the DMD gene, resulting in the dysfunction of dystrophin. We generated an induced pluripotent stem cell (iPSC) from a patient with DMD carrying exon 51 deletion in the DMD gene. This iPSC line can serve as a model for studying the pathogenesis and therapeutics of DMD.

CCR2 improves homing and engraftment of adipose-derived stem cells in dystrophic mice.

BACKGROUND: Dystrophinopathy, a common neuromuscular disorder caused by the absence of dystrophin, currently lacks effective treatments. Systemic transplantation of adipose-derived stem cells (ADSCs) is a promising treatment approach, but its low efficacy remains a challenge. Chemokine system-mediated stem cell homing plays a critical role in systemic transplantation. Here, we investigated whether overexpression of a specific chemokine receptor could improve muscle homing and therapeutic effects of ADSC systemic transplantation in dystrophic mice. METHODS: We analysed multiple microarray datasets from the Gene Expression Omnibus to identify a candidate chemokine receptor and then evaluated the protein expression of target ligands in different tissues and organs of dystrophic mice. The candidate chemokine receptor was overexpressed using the lentiviral system in mouse ADSCs, which were used for systemic transplantation into the dystrophic mice, followed by evaluation of motor function, stem cell muscle homing, dystrophin expression, and muscle pathology. RESULTS: Chemokine-profile analysis identified C-C chemokine receptor (CCR)2 as the potential target for improving ADSC homing. We found that the levels of its ligands C-C chemokine ligand (CCL)2 and CCL7 were higher in muscles than in other tissues and organs of dystrophic mice. Additionally, CCR2 overexpression improved ADSC migration ability and maintained their multilineage-differentiation potentials. Compared with control ADSCs, transplantation of those overexpressing CCR2 displayed better muscle homing and further improved motor function, dystrophin expression, and muscle pathology in dystrophic mice. CONCLUSIONS: These results demonstrated that CCR2 improved ADSC muscle homing and therapeutic effects following systemic transplantation in dystrophic mice.

In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers.

BACKGROUND: Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. METHODS: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. RESULTS: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member ß-dystroglycan. CONCLUSIONS: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

Self-Compliance and High Performance Pt/HfOx/Ti RRAM Achieved through Annealing.

A self-compliance resistive random access memory (RRAM) achieved through thermal annealing of a Pt/HfOx/Ti structure. The electrical characteristic measurements show that the forming voltage of the device annealing at 500 °C decreased, and the switching ratio and uniformity improved. Tests on the device's cycling endurance and data retention characteristics found that the device had over 1000 erase/write endurance and over 105 s of lifetime (85 °C). The switching mechanisms of the devices before and after annealing were also discussed.

Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients.

Background: Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive muscle disorder characterized by heterogeneous progression and severity. We aimed to study the effects of single nucleotide polymorphisms (SNPs) in SPP1 and LTBP4 on DMD progression in Chinese patients. Methods: We genotyped LTBP4 haplotypes and the SPP1 promoter SNPs rs28357094, rs11730582, and rs17524488 in 326 patients registered in the neuromuscular database of The First Affiliated Hospital of Sun Yat-sen University. Kaplan-Meier curves and log-rank tests were used to estimate and compare median age at loss of ambulation, while Cox proportional hazard regression models were used as to analyze the effects of glucocorticoids treatments, DMD genotype, and SPP1/LTBP4 SNPs on loss of ambulation. Results: The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (p = 0.006), with hazard ratio 0.63 (p = 0.008), in patients with truncated DMD genotype and undergoing steroid treatment. On the other hand, rs17524488 in SPP1 and the IAAM/IAAM haplotype in LTBP4 were not associated with time to ambulation loss. Conclusions: SPP1 rs11730582 is a genetic modifier of the long-term effects of steroid treatment in Chinese DMD patients. Thus, any future clinical study in DMD should adjust for glucocorticoids use, DMD genotype, and SPP1 polymorphisms.

Genotypes and Phenotypes of DMD Small Mutations in Chinese Patients With Dystrophinopathies.

Dystrophinopathies are a group of neuromuscular disorders resulting from mutations in DMD, including Duchenne muscular dystrophy (DMD), intermediate muscular dystrophy (IMD), and Becker muscular dystrophy (BMD). Herein, we present the characteristics of small mutations in Chinese patients with dystrophinopathies, and explore genotype-phenotype correlations. In our cohort, 115 patients with small mutations (18.49% of all patients) were included and DMD mutations were detected by either Sanger (53.91%) or next generation sequencing (46.09%). In total, 106 small mutations were detected, 28 of which (26.42%) had not been reported previously. The most common mutations were nonsense mutations (52.17%), followed by splicing (24.35%), frameshift (17.39%), and missense mutations (5.22%), in addition to a single untranslated region mutation (0.87%). We discovered distinct mutation characteristics in our patients, such as different positional distributions, indicating different exon skipping therapy strategies for small mutations in Chinese patients. Almost all patients (96.51%) with truncating or missense mutations, were covered by triple/double/single-exon skipping therapy; the most frequent single-exon skipping strategy was skipping exon 32, applicable for 8.51% of patients. Furthermore, splicing classification grades were correlated with phenotypes in nonsense mutations (P < 0.001), and serum creatinine levels differed significantly between DMD/IMD and BMD for patients ≤ 16 years old (P = 0.002). These observations can further aid prognostic judgment and guide treatment. In conclusion, the mutation characteristics and genotype-phenotype correlations in Chinese patients with dystrophinopathies and small mutations could provide insights into the molecular mechanisms of pathogenesis, diagnosis, and treatment designs.

HLA Polymorphism Affects Risk of de novo Mutation of dystrophin Gene and Clinical Severity of Duchenne Muscular Dystrophy in a Southern Chinese Population.

Immune-mediated pathology has been thought to be an important factor contributing to Duchenne muscular dystrophy (DMD). Allele frequencies of certain HLA types are known to differ between patients with dystrophinopathies and healthy controls with low-resolution HLA gene typing data in limit reports. Using Polymerase chain reactionsequence based typing (PCR-SBT) to genotype 64 children with DMD in HLA-A, -B,-C, -DRB1, and -DQB1 locus and 503 healthy controls in HLA-A, -B, -DRB1 locus, this study aimed to investigate associations of specific HLA alleles with, and their possible roles in the development and clinical phenotypic severity of DMD. The χ2 test was used to evaluate the distribution of allele frequencies in HLA-A, -B, -DRB1 locus between the patients and healthy controls. A significantly higher frequency of HLA-B * 07:05 was found in children with DMD compared to that in controls (OR = 16.2, 95%CI = 2.9-89.3, P < 0.046). More importantly, significantly higher frequencies of HLA-A * 29:01 (OR = 77.308, 95%CI = 6.794-879.731, P < 0.0160) and HLA-B *07:05 (OR = 60.240, 95%CI = 9.637-376.535, P < 2.41*10-3) was found in patients with de novo mutations (n = 14) compared to controls while no difference of HLA alleles frequency ware indicated between patients with inherited mutation and control. The result indicates that HLA alleles is associated with pathogenesis of DMD especially DMD with de novo mutation. We use Vignos scale to estimate the lower limb motor function of patients. The impact of HLA alleles on score of Vignos scale of DMD children was estimated by multiple linear regression. Our study indicates that HLA-A *02:01 may have a dampening effect on the clinical phenotypic severity of DMD, evidenced by the presence of HLA-A *02:01 being associated with lower Vignos score. Our study demonstrates that certain HLA alleles are indeed associated with the pathogenesis and clinical phenotypic severity of DMD.

Ratio of Creatine Kinase to Alanine Aminotransferase as a Biomarker of Acute Liver Injury in Dystrophinopathy.

OBJECTIVE: To investigate the ratios of creatine kinase (CK) to aminotransferases as biomarkers of acute liver injury in dystrophinopathy. METHODS: C57 and mdx (dystrophic) mice were treated with a hepatotoxic reagent D-galactosamine (D-GalN). The degrees of liver and muscle injury were assessed using histological examinations. To examine whether serum CK-adjusted aminotransferase levels could indicate liver status in dystrophic mice, the CK/alanine aminotransferase (ALT) and CK/aspartate aminotransferase (AST) ratios were analyzed. Furthermore, we enrolled 658 male patients with dystrophinopathy and 378 male patients without muscle and liver injury as control, whose serum ALT, AST, and CK levels were examined. RESULTS: Animal experiments indicated that D-GalN treatment could induce acute liver injury but not muscle injury. Additionally, D-GalN decreased the CK/ALT and CK/AST ratios in both C57 mice and mdx mice (P < 0.001). However, there was an overlap of the CK/AST ratio between dystrophic mice with and without acute liver injury. In patients with dystrophinopathy, CK-adjusted ALT diminished the variability associated with age, genotype, clinical phenotype, and motor function (P > 0.05). CONCLUSIONS: CK/ALT is a potential biomarker for the differential evaluation of acute liver injury in dystrophic mice, which highlights the value to further evaluate the practice of CK/ALT in dystrophinopathy patients.

The clinical spectrum and genetic variability of limb-girdle muscular dystrophy in a cohort of Chinese patients.

BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a commonly diagnosed hereditary muscular disorder, characterized by the progressive weakness of the limb-girdle muscles. Although the condition has been well-characterized, clinical and genetic heterogeneity can be observed in patients with LGMD. Here, we aimed to describe the clinical manifestations and genetic variability among a cohort of patients with LGMD in South China. RESULTS: We analyzed the clinical information, muscle magnetic resonance imaging (MRI) findings, and genetic results obtained from 30 patients (24 families) with clinically suspected LGMD. In 24 probands, 38 variants were found in total, of which 18 were shown to be novel. Among the 30 patients, the most common subtypes were dysferlinopathy in eight (26.67%), sarcoglycanopathies in eight [26.67%; LGMD 2C in three (10.00%), LGMD 2D in three (10.00%), and LGMD 2F in two (6.67%)], LGMD 2A in seven (23.33%), followed by LGMD 1B in three (10.00%), LGMD 2I in three (10.00%), and early onset recessive Emery-Dreifuss-like phenotype without cardiomyopathy in one (3.33%). Furthermore, we also observed novel clinical presentations for LGMD 1B, 2F, and 2I patients with hypermobility of the joints in the upper limbs, a LGMD 2F patient with delayed language development, and other manifestations. Moreover, distinct distributions of fatty infiltration in patients with LGMD 2A, dysferlinopathy, and the early onset recessive Emery-Dreifuss-like phenotype without cardiomyopathy were also observed based on muscle MRI results. CONCLUSIONS: In this study, we expanded the clinical spectrum and genetic variability found in patients with LGMD, which provided additional insights into genotype and phenotype correlations in this disease.

Social implications of fission in wild Formosan macaques at Mount Longevity, Taiwan.

Group fission in non-human primates has long been proposed to result from interactions between ecological and social factors. Several studies have documented possible causes for group fission, but its proximate causes and ultimate adaptive values are not yet fully understood. We have examined the existing hypotheses on fission from long-term demographic data of Formosan macaques inhabiting the lowland rainforest at Mt Longevity, Taiwan. Five cases of fission occurred in four social groups. We have recorded two types of fission: one involving the separation of a high-ranking adult male and multiple adult females, the other initiated by adult females from main groups. Five adult females immigrated and emigrated a few times between the main and branch groups (oscillation) in three fission events. Data presented in this study are consistent with the prediction that low-ranking females split from main groups when their fitness costs increase due to ecological pressure or population growth. However, their reproductive success may decrease after fission due to a high rate of intra-group competition. Nevertheless, it is beneficial for males to be involved in fission since this increases reproductive benefits by decreasing the sex ratio in small newly formed groups.