On the Improvement of China’s Community Correction

As a non-imprisonment penalty opposite to imprisonment penalty, communist correction is in line with the requirement of China’s socialist construction and international human rights doctrine. The evolution of China’s community correction experienced two stages of trial and full establishment. Based on a comparative analysis of the United States community correction system, this article will put forward recommendations for the improvement of China’s community correction system from three aspects: legislation, law enforcement and financial guarantee

A Comparative Study of the Prosecution Qualification of Public Interest Litigation

In the middle of the 20th century, with the constant emergence of various public interest damage cases such as environmental pollution, infringement of consumer rights and interests, etc., every country in the world was exploring to establish a mode of litigation that would be different from the traditional private interest litigation, public interest litigation thus emerged as the times required. In the 21st century today, no matter in the countries of the common law system or the continental law system, they are all perfecting the corresponding public interest litigation system combining their own country’s actual situation. In comparison, our country’s regulation for the prosecution qualification of public interest litigation is still imperfect. This article thus tries to propose some suggestions for this situation from three aspects, i.e., enlarging the subject range for the prosecution of infringement of consumer rights and interests, exerting the main force of procuratorate, and increasing public participation

Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets

OPA1 +/− -iPSCs (OL) are unfavorable to differentiate into neural rosette. Culture conditions were the same as those in Fig. 3. Panel A shows day 5 EBs, which were derived from control and OL-iPSCs, respectively. Morphologically, OL-EBs look similar to control EBs. Panel B shows neuron rosettes (NRs) after 5 days of EB attachment. Fewer and smaller neuron rosettes were derived from OL-EBs, compared with neuron rosettes from control EBs. Figure S2 OPA1 +/− -iPSCs (OL) failed to differentiate into RGCs with culture medium supplemented with 10 % FBS and DAPT. Differentiation method in Fig. 4 was followed. Putative RGCs were fixed on day 24 before fixation, followed by IF staining. Upper panel shows staining of TUJ1 (green) and BRN3a (red), while lower panel displays staining of TUJ1 (green) and ISLET1 (red). The scale bars equal 50 μM. Figure S3 IF analysis of RGCs derived from the control and VO-iPSCs on day 38. Neurospheres were plated onto PLO/L-coated plates and cultured in hESC medium containing 10 μM DAPT and 10 % FBS for 21 days before fixation with 4 % PFA on day 38. Cells were stained with TUJ1 (green), BRN3a (red) and ISLET-1 (red) antibodies. The scale bars equal 20 μM. Figure S4 NIM promoted OPA1 +/− -RGC (OL) generation detected by IF. Putative OL-RGCs derived from OL-iPSCs were cultured with hESC medium containing 10 μM DAPT, 10 % FBS, and 10 % neural induction medium (NIM) for 14 days before fixation on day 31. Upper panel shows TUJ1 (green) and BRN3a (red) staining. Lower panel shows staining of TUJ1 (green) and ISLET1 (red). The scale bars equal 50 μM. Figure S5 Quantification of RGC differentiation efficiency. The culture medium used for RGC differentiation contained 10 % neural induction medium. Samples were normalized to the control BRN3a/DAPI staining or the control ISLET-1/DAPI staining. The number of BRN3a or ISLET-1 signals versus the number of DAPI signals was calculated. A p-value of 0.084 was obtained for the BRN3a signal comparison between the control and VO, and a p-value of 0.076 was obtained for the ISLET-1 signal comparison between the control and VO. Student’s t-test was used to analyze differences between two groups. Figure S6 Noggin rescued OPA1 +/− -iPSC (OL) differentiation into RGCs confirmed by IF. Mature EBs were cultured with hES medium containing 10 % FBS and 100 ng/mL Noggin to obtain neuron rosettes, followed by culturing putative RGCs with hES medium containing 10 % FBS, DAPT and 100 ng/mL Noggin. Cells were fixed with 4 % PFA on day 31. Upper panel shows IF staining of TUJ-1 (green) and BRN3a (red), whereas lower panel shows staining of TUJ-1 (green) and ISLET1 (red). The scale bars equal 50 μM in both panels. Figure S7 Addition of 17β-estradiol in RGC differentiation medium promoted generation of OPA1 +/− -RGCs (OL). Putative RGCs were incubated with 100 nM 17β-estradiol in the cell culture medium during all of the differentiation stages, followed by fixation on day 31. Upper panel shows IF staining against TUJ1 (green) and BRN3a (red). Lower panel shows TUJ1 (green) and ISLET-1 (red) staining. The scale bars equal 50 μM. (PPTX 12904 kb

The Deafness-Associated Mitochondrial DNA Mutation at Position 7445, Which Affects tRNASer(UCN) Precursor Processing, Has Long-Range Effects on NADH Dehydrogenase Subunit ND6 Gene Expression

The pathogenetic mechanism of the deafness-associated mitochondrial DNA (mtDNA) T7445C mutation has been investigated in several lymphoblastoid cell lines from members of a New Zealand pedigree exhibiting the mutation in homoplasmic form and from control individuals. We show here that the mutation flanks the 3' end of the tRNASer(UCN) gene sequence and affects the rate but not the sites of processing of the tRNA precursor. This causes an average reduction of ~70% in the tRNASer(UCN) level and a decrease of ~45% in protein synthesis rate in the cell lines analyzed. The data show a sharp threshold in the capacity of tRNASer(UCN) to support the wild-type protein synthesis rate, which corresponds to ~40% of the control level of this tRNA. Strikingly, a 7445 mutation-associated marked reduction has been observed in the level of the mRNA for the NADH dehydrogenase (complex I) ND6 subunit gene, which is located ~7 kbp upstream and is cotranscribed with the tRNASer(UCN) gene, with strong evidence pointing to a mechanistic link with the tRNA precursor processing defect. Such reduction significantly affects the rate of synthesis of the ND6 subunit and plays a determinant role in the deafness-associated respiratory phenotype of the mutant cell lines. In particular, it accounts for their specific, very significant decrease in glutamate- or malate-dependent O2 consumption. Furthermore, several homoplasmic mtDNA mutations affecting subunits of NADH dehydrogenase may play a synergistic role in the establishment of the respiratory phenotype of the mutant cells

Human Mitochondrial tRNA Mutations in Maternally Inherited Deafness

AbstractMutations in mitochondrial tRNA genes have been shown to be associated with maternally inherited syndromic and non-syndromic deafness. Among those, mutations such as tRNALeu(UUR)3243A>G associated with syndromic deafness are often present in heteroplasmy, and the non-syndromic deafness-associated tRNA mutations including tRNASer(UCN)7445A>G are often in homoplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary factors underlying the development of hearing loss. However, other tRNA mutations such as tRNAThr15927G>A and tRNASer(UCN)7444G>A are insufficient to produce a deafness phenotype, but always act in synergy with the primary mitochondrial DNA mutations, and can modulate their phenotypic manifestation. These tRNA mutations may alter the structure and function of the corresponding mitochondrial tRNAs and cause failures in tRNAs metabolism. Thereby, the impairment of mitochondrial protein synthesis and subsequent defects in respiration caused by these tRNA mutations, results in mitochondrial dysfunctions and eventually leads to the development of hearing loss. Here, we summarized the deafness-associated mitochondrial tRNA mutations and discussed the pathophysiology of these mitochondrial tRNA mutations, and we hope these data will provide a foundation for the early diagnosis, management, and treatment of maternally inherited deafness

A Network Coding Based Routing Protocol for Underwater Sensor Networks

Due to the particularities of the underwater environment, some negative factors will seriously interfere with data transmission rates, reliability of data communication, communication range, and network throughput and energy consumption of underwater sensor networks (UWSNs). Thus, full consideration of node energy savings, while maintaining a quick, correct and effective data transmission, extending the network life cycle are essential when routing protocols for underwater sensor networks are studied. In this paper, we have proposed a novel routing algorithm for UWSNs. To increase energy consumption efficiency and extend network lifetime, we propose a time-slot based routing algorithm (TSR).We designed a probability balanced mechanism and applied it to TSR. The theory of network coding is introduced to TSBR to meet the requirement of further reducing node energy consumption and extending network lifetime. Hence, time-slot based balanced network coding (TSBNC) comes into being. We evaluated the proposed time-slot based balancing routing algorithm and compared it with other classical underwater routing protocols. The simulation results show that the proposed protocol can reduce the probability of node conflicts, shorten the process of routing construction, balance energy consumption of each node and effectively prolong the network lifetime

Functional characterization of the mitochondrial 12S rRNA C1494T mutation associated with aminoglycoside-induced and non-syndromic hearing loss

In this study, we report the biochemical characterization of the deafness-associated mitochondrial 12S rRNA C1494T mutation using 27 cybrid cell lines constructed by transferring mitochondria from 9 lymphoblastoid cell lines derived from a Chinese family into human mitochondrial DNA (mtDNA)-less (ρ°) cells. Six cybrids derived from two asymptomatic members, and nine cybrids derived from three symptomatic members of the Chinese family carrying the C1494T mutation exhibited ∼38 and 43% decrease in the rate of mitochondrial protein labeling, respectively, compared with twelve cybrids derived from four Chinese control individuals. These defects are apparently a primary contributor to significant reductions in the rate of overall respiratory capacity or the rate of malate/glutamate promoted respiration, or succinate/G3P-promoted respiration, or TMPD/ascorbate-promoted respiration in mutant cybrid cell lines derived from either symptomatic or asymptomatic individuals. Furthermore, the very significant/nearly identical increase in the ratio of doubling times in DMDM medium in the presence/absence of high concentration of paromomycin was observed in symptomatic or asymptomatic cybrid cell lines carrying the C1494T mutation as compared with the average rate in control cell lines. These observations provide the direct biochemical evidences that the C1494T mutation is a pathogenic mtDNA mutation associated with aminoglycoside-induced and non-syndromic hearing loss. In addition, these data provide the first biochemical evidence that nuclear background plays a critical role in the phenotypic manifestation of non-syndromic hearing loss and aminoglycoside toxicity associated with the C1494T mutation

Mitochondrial Stress Engages E2F1 Apoptotic Signaling to Cause Deafness

SummaryMitochondrial dysfunction causes poorly understood tissue-specific pathology stemming from primary defects in respiration, coupled with altered reactive oxygen species (ROS), metabolic signaling, and apoptosis. The A1555G mtDNA mutation that causes maternally inherited deafness disrupts mitochondrial ribosome function, in part, via increased methylation of the mitochondrial 12S rRNA by the methyltransferase mtTFB1. In patient-derived A1555G cells, we show that 12S rRNA hypermethylation causes ROS-dependent activation of AMP kinase and the proapoptotic nuclear transcription factor E2F1. This retrograde mitochondrial-stress relay is operative in vivo, as transgenic-mtTFB1 mice exhibit enhanced 12S rRNA methylation in multiple tissues, increased E2F1 and apoptosis in the stria vascularis and spiral ganglion neurons of the inner ear, and progressive E2F1-dependent hearing loss. This mouse mitochondrial disease model provides a robust platform for deciphering the complex tissue specificity of human mitochondrial-based disorders, as well as the precise pathogenic mechanism of maternally inherited deafness and its exacerbation by environmental factors.PaperFlic