Gene Variant of Barrier to Autointegration Factor 2 (Banf2w) Is Concordant with Female Determination in Cichlids

Oreochromis fishes exhibit variability of sex-determination (SD) genes whose characterization contributes to understanding of the sex differentiation network, and to effective tilapia farming, which requires all-male culture. However, O. niloticus (On) amh is the only master-key regulator (MKR) of SD that has been mapped (XY/XX SD-system on LG23). In O. aureus (Oa), LG3 controls a WZ/ZZ SD-system that has recently been delimited to 9.2 Mbp, with an embedded interval rich with female-specific variation, harboring two paics genes and banf2. Developing genetic markers within this interval and using a hybrid Oa stock that demonstrates no recombination repression in LG3, we mapped the critical SD region to 235 Kbp on the orthologous On physical map (p < 1.5 × 10⁻²⁶). DNA-seq assembly and peak-proportion analysis of variation based on Sanger chromatograms allowed the characterization of copy-number variation (CNV) of banf2. Oa males had three exons capable of encoding 90-amino-acid polypeptides, yet in Oa females, we found an extra copy with an 89-amino-acid polypeptide and three non-conservative amino acid substitutions, designated as banf2w. CNV analysis suggested the existence of two to five copies of banf2 in diploidic Cichlidae. Disrupting the Hardy–Weinberg equilibrium (p < 4.2 × 10⁻³), banf2w was concordant with female determination in Oa and in three cichlids with LG3 WZ/ZZ SD-systems (O. tanganicae, O. hornorum and Pelmatolapia mariae). Furthermore, exclusive RNA-seq expression in Oa females strengthened the candidacy of banf2w as the long-sought LG3 SD MKR. As banf genes mediate nuclear assembly, chromatin organization, gene expression and gonad development, banf2w may play a fundamental role inducing female nucleus formation that is essential for WZ/ZZ SD.     

Investigating LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

LMNA-related dilated cardiomyopathy is an inherited heart disease caused by mutations in the LMNA gene encoding for lamin A/C. The disease is characterized by left ventricular enlargement and impaired systolic function associated with conduction defects and ventricular arrhythmias. We hypothesized that LMNA-mutated patients’ induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) display electrophysiological abnormalities, thus constituting a suitable tool for deciphering the arrhythmogenic mechanisms of the disease, and possibly for developing novel therapeutic modalities. iPSC-CMs were generated from two related patients (father and son) carrying the same E342K mutation in the LMNA gene. Compared to control iPSC-CMs, LMNA-mutated iPSC-CMs exhibited the following electrophysiological abnormalities: (1) decreased spontaneous action potential beat rate and decreased pacemaker current (I_f) density; (2) prolonged action potential duration and increased L-type Ca²⁺ current (I_Ca,L) density; (3) delayed afterdepolarizations (DADs), arrhythmias and increased beat rate variability; (4) DADs, arrhythmias and cessation of spontaneous firing in response to β-adrenergic stimulation and rapid pacing. Additionally, compared to healthy control, LMNA-mutated iPSC-CMs displayed nuclear morphological irregularities and gene expression alterations. Notably, KB-R7943, a selective inhibitor of the reverse-mode of the Na⁺/Ca²⁺ exchanger, blocked the DADs in LMNA-mutated iPSC-CMs. Our findings demonstrate cellular electrophysiological mechanisms underlying the arrhythmias in LMNA-related dilated cardiomyopathy.     

Control-relevant models for glucose control using a priori patient characteristics

One of the difficulties in the development of a reliable artificial pancreas for people with type 1 diabetes mellitus (T1DM) is the lack of accurate models of an individual's response to insulin. Most control algorithms proposed to control the glucose level in subjects with T1DM are model-based. Avoiding postprandial hypoglycemia ( 60 mg/dl) while minimizing prandial hyperglycemia ( > 180 mg/dl) has shown to be difficult in a closed-loop setting due to the patient-model mismatch. In this paper, control-relevant models are developed for T1DM, as opposed to models that minimize a prediction error. The parameters of these models are chosen conservatively to minimize the likelihood of hypoglycemia events. To limit the conservatism due to large intersubject variability, the models are personalized using a priori patient characteristics. The models are implemented in a zone model predictive control algorithm. The robustness of these controllers is evaluated in silico, where hypoglycemia is completely avoided even after large meal disturbances. The proposed control approach is simple and the controller can be set up by a physician without the need for control expertise.     

4G移动设备需要可编程性

到2013年,移动宽带用户(使用W-CMDA、EV-DO、HSPA、HSPA+、LTE、TD-LTE和移动WiMAX)的数目预计将会超过20亿;在2015年之前,单单LTE的用户数就可望达到4.4亿。下一代无线宽带需求持续的增长,也使得复杂性向上攀升到另一     

Eradication of Multi‐Drug Resistant Bacteria by a Novel Zn‐doped CuO Nanocomposite

Zinc‐doped copper oxide nanoparticles are synthesized and simultaneously deposited on cotton fabric using ultrasound irradiation. The optimization of the processing conditions, the specific reagent ratio, and the precursor concentration results in the formation of uniform nanoparticles with an average size of ≈30 nm. The antibacterial activity of the Zn‐doped CuO Cu_0.88Zn_0.12O in a colloidal suspension or deposited on the fabric is tested against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) bacteria. A substantial enhancement of 10 000 times in the antimicrobial activity of the Zn–CuO nanocomposite compared to the pure CuO and ZnO nanoparticles (NPs) is observed after 10 min exposure to the bacteria. Similar activities are observed against multidrug‐resistant bacteria (MDR), (i.e., Methicillin‐resistant S. aureus and MDR E. coli) further emphasizing the efficacy of this composite. Finally, the mechanism for this enhanced antibacterial activity is presented.     

Toward a redefinition of implicit memory: Process dissociations following elaborative processing and self-generation.

Does conceptual processing affect unconscious uses of memory? The authors used a process-dissociation procedure to separate automatic (unconscious) and consciously controlled uses of memory in a stem-completion task. Contrary to results from indirect test conditions, estimates derived from the procedure showed no effect of self-generation and no differential effect of semantic and nonsemantic study conditions on automatic uses of memory. These results provide evidence that (1) indirect tests are often contaminated by conscious uses of memory and (2) stem completion is highly dependent on prior perceptual (and perhaps lexical) processing. The experiments demonstrate the advantages of using process-dissociation procedures over comparisons between direct and indirect tests. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bioenergetic and Metabolic Impairments in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Duchenne Muscular Dystrophy Patients

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene and dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality in DMD patients. We tested the hypothesis that DCM is caused by metabolic impairments by employing induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from four DMD patients; an adult male, an adult female, a 7-year-old (7y) male and a 13-year-old (13y) male, all compared to two healthy volunteers. To test the hypothesis, we measured the bioenergetics, metabolomics, electrophysiology, mitochondrial morphology and mitochondrial activity of CMs, using respirometry, LC–MS, patch clamp, electron microscopy (EM) and confocal microscopy methods. We found that: (1) adult DMD CMs exhibited impaired energy metabolism and abnormal mitochondrial structure and function. (2) The 7y CMs demonstrated arrhythmia-free spontaneous firing along with “healthy-like” metabolic status, normal mitochondrial morphology and activity. In contrast, the 13y CMs were mildly arrhythmogenic and showed adult DMD-like bioenergetics deficiencies. (3) In DMD adult CMs, mitochondrial activities were attenuated by 45–48%, whereas the 7y CM activity was similar to that of healthy CMs. (4) In DMD CMs, but not in 7y CMs, there was a 75% decrease in the mitochondrial ATP production rate compared to healthy iPSC-CMs. In summary, DMD iPSC-CMs exhibit bioenergetic and metabolic impairments that are associated with rhythm disturbances corresponding to the patient’s phenotype, thereby constituting novel targets for alleviating cardiomyopathy in DMD patients.     

Mode I interlaminar fracture toughness of Nylon 66 nanofibrilmat interleaved carbon/epoxy laminates

Carbon/epoxy laminates interleaved with laboratory scale electrospun Nylon 66 nanofibrilmat and spunbonded nonwoven mats were investigated. The effect of the nanoscale fibers on the fracture toughness of the composite under pure Mode I loading was evaluated. It was shown that the nanofibrilmat is responsible for a major interlaminar fracture toughness improvement, as high as 255–322%, compared to a noninterleaved carbon/epoxy reference laminate. We further studied the improvement mechanism of the electrospun nanofibrilmat compared to a commercial spunbonded nonwoven Nylon 66 mat. A combination of two interlayer fracture mechanisms responsible for the toughness improvement is suggested: the first is related to the high energy dissipated by bridged thermoplastic nanofibers and the second is attributed to the generation of a plastic zone near the crack tip. The interlaminar fracture mechanisms of both electrospun nanofibrilmat and the nonwoven mat interleaving was analyzed and discussed. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers