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Using a narratological synchronic reading, this article argues that Reuben and Judah are contrastively juxtaposed in their rhetoric and intentions in Genesis 37. Reuben considers the brothers’ plot a criminal act and bans both their internal intentions and their external evildoings against Joseph, whereas Judah repeatedly forbids them from killing Joseph, their own brother, posing a moral argument against fratricide. Problematically, however, he permits another evildoing, the sale of their own brother. The contrastive parallel of the two brothers in Genesis 37 does not support the classic documentary hypothesis, nor the supplementary expansion in favour of Judah. Rather, Judah’s problematic dealings with his own brother harkens to the practice of selling of own “flesh” and “kindred” into slavery in the post-exilic period. Genesis 37 in its present position provides a natural link to Genesis 38, as both chapters are identical in their negative depiction of Judah.

Huntington’s disease (HD) is a severe inherited neurological disorder caused by a CAG repeat expansion in the huntingtin gene (HTT), leading to the accumulation of mutant huntingtin with polyglutamine repeats. Despite its severity, there is no cure for this debilitating disease. HTT lowering strategies, including antisense oligonucleotides (ASO) showed promising results very recently. Attempts to develop stem cell-based therapeutics have shown efficacy in preclinical HD models. Using an HD patient’s autologous cells, which have genetic defects, may hamper therapeutic efficacy due to mutant HTT. Pretreating these cells to reduce mutant HTT expression and transcription may improve the transplanted cells’ therapeutic efficacy. To investigate this, we targeted the SUPT4H1 gene that selectively supports the transcription of long trinucleotide repeats. Transplanting SUPT4H1-edited HD-induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) into the YAC128 HD transgenic mouse model improved motor function compared to unedited HD iPSC-NPCs. Immunohistochemical analysis revealed reduced mutant HTT expression without compensating wild-type HTT expression. Further, SUPT4H1 editing increased neuronal and decreased reactive astrocyte differentiation in HD iPSC-NPCs compared to the unedited HD iPSC-NPCs. This suggests that ex vivo editing of SUPT4H1 can reduce mutant HTT expression and provide a therapeutic gene editing strategy for autologous stem cell transplantation in HD.

Thyroid hormone (TH) has long been believed to play a minor role in male reproduction. However, evidences from experimental model of thyrotoxicosis or hypothyroidism suggests its role in spermatogenesis. Cellular action of TH requires membrane transport via specific transporters such as monocarboxylate transporter 8 (MCT8). SLC16A2 (encodes for MCT8) inactivating mutation in humans can lead to Allan-Herndon Dudley-syndrome, a X-linked psychomotor and growth retardation. These patients present cryptorchidism which suggests a role of MCT8 during spermatogenesis. In this study, we found that Mct8 is highly expressed during early postnatal development and decreases its expression in the adulthood of testis of wild-type male rats. Histological analysis revealed that spermatogonia largely lacks MCT8 expression while spermatocytes and maturing spermatids highly express MCT8. To further understand the role of Mct8 during spermatogenesis, we generated Slc16a2 (encodes MCT8) knockout rats using CRISPR/Cas9. Serum THs (T3 and T4) level were significantly altered in Slc16a2 knockout rats when compared to wild-type littermates during early to late postnatal development. Unlike Slc16a2 knockout mice, Slc16a2 knockout rats showed growth delay during early to late postnatal development. In adult Slc16a2 knockout rats, we observed reduced sperm motility and viability. Collectively, our data unveil a functional involvement of MCT8 in spermatogenesis, underscoring the importance of TH signaling and action during spermatogenesis.

The Streptococcus pyogenes CRISPR/Cas9 (SpCas9) system is now widely utilized to generate genome engineered mice; however, some studies raised issues related to off-target mutations with this system. Herein, we utilized the Campylobacter jejuni Cas9 (CjCas9) system to generate knockout mice. We designed sgRNAs targeting mouse Tyr or Foxn1 and microinjected into zygotes along with CjCas9 mRNA. We obtained newborn mice from the microinjected embryos and confirmed that 50% (Tyr) and 38.5% (Foxn1) of the newborn mice have biallelic mutation on the intended target sequences, indicating efficient genome targeting by CjCas9. In addition, we analyzed off-target mutations in founder mutant mice by targeted deep sequencing and whole genome sequencing. Both analyses revealed no off-target mutations at potential off-target sites predicted in silico and no unexpected random mutations in analyzed founder animals. In conclusion, the CjCas9 system can be utilized to generate genome edited mice in a precise manner., Highlights • Generate genetically engineered mice using the Campylobacter jejuni Cas9 (CjCas9) system. • CjCas9 showed reasonably high biallelic InDel mutation rate (up to 50%) in newborn mice. • CjCas9 system showed relatively higher specificity compared to SpCas9 system.

The CRISPR/Cas9 system is widely applied in genome engineering due to its simplicity and versatility. Although this has revolutionized genome-editing technology, knockin animal generation via homology directed repair (HDR) is not as efficient as nonhomologous end-joining DNA-repair-dependent knockout. Although its double-strand break activity may vary, Cas9 derived from Streptococcus pyogenens allows robust design of single-guide RNAs (sgRNAs) within the target sequence; However, prescreening for different sgRNA activities delays the process of transgenic animal generation. To overcome this limitation, multiple sets of different sgRNAs were examined for their knockin efficiency. We discovered profound advantages associated with single-stranded oligo-donor-mediated HDR processes using overlapping sgRNAs (sharing at least five base pairs of the target sites) as compared with using non-overlapping sgRNAs for knock-in mouse generation. Studies utilizing cell lines revealed shorter sequence deletions near target mutations using overlapping sgRNAs as compared with those observed using non-overlapping sgRNAs, which may favor the HDR process. Using this simple method, we successfully generated several transgenic mouse lines harboring loxP insertions or single-nucleotide substitutions with a highly efficiency of 18–38%. Our results demonstrate a simple and efficient method for generating transgenic animals harboring foreign-sequence knockins or short-nucleotide substitutions by the use of overlapping sgRNAs., Genome editing: Improving efficiency by improving DNA repair A method to improve the efficiency of repairing double-stranded DNA breaks facilitates the production of animals with edited genomes. The CRISPR/Cas9 system has been revolutionising biomedical research as it allows the insertion or deletion of any DNA sequence at specific sites by making double-strand DNA breaks. However, the insertion of precise genetic changes is limited by the relatively low efficiency of the repair mechanism, which requires a template DNA molecule to promote error-free repair of the DNA strands. A team of South Korean scientists led by Su Cheong Yeom at Seoul National University and Han Woong Lee at Yonsei University show that delivering multiple overlapping single-guide RNAs (that share at least five base pairs of the target sequence) as a DNA template significantly improves the repair and thus the production of mice with a targeted gene insertion.

배경 및 목적 : 본 연구는 학령기 아동의 글쓰기에 나타난 비유언어(직유, 은유, 관용어)가 담화유형(묘사담화, 이야기담화) 및 학년(2, 4, 6)에 따라 어떠한 사용 양상을 보이는지, 비유언어의 사용 비율은 담화길이(T-unit, NTW)나 어휘다양도(NDW, MLT-dw)와 어떠한 상관관계를 보이는지 파악하고자 하였다. 방법: 서울 소재 초등학교에...

배경 및 목적: 본 연구에서는 관용어 유형(감정표현, 행위표현)과 친숙도(고, 저)에 따른 학령기 고기능 자폐스펙트럼장애 아동과 일반 아동 간의 관용어 이해 정확도에 유의한 차이가 있는지 살펴보고, 집단 내에서 오류 유형에 따른 오답률에 유의한 차이가 있는지 살펴보고자 하였다. 방법: 동작성 지능과 언어발달이 정상 범위에 있는 학령기 고기능 자폐스펙트럼장애...

The reason underlying God’s divergent actions towards the offerings of Cain and Abel has been highly disputed. It has been often assumed that the reason mainly lies in the two offerers’ differing dispositions and attitudes or in the quality and character of their offerings. However, the close relationship between YHWH and Cain and the differences between the text’s descriptions of Cain and of Abel provide a more concrete rationale for God’s action: Through the seemingly unjust rejection of Cain’s offering, YHWH calls on him to recognize his relationship and responsibility for his inferior brother. That the relation to others is inseparable from the relation to God becomes evident once more in the punishment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

KO mice provide an excellent tool to determine roles of specific genes in biomedical filed. Traditionally, knockout mice were generated by homologous recombination in embryonic stem cells. Recently, engineered nucleases, such as zinc finger nuclease, transcription activator-like effector nuclease and clustered regularly interspaced short palindromic repeats (CRISPR), were used to produce knockout mice. This new technology is useful because of high efficiency and ability to generate biallelic mutation in founder mice. Until now, most of knockout mice produced using engineered nucleases were C57BL/6 strain. In the present study we used CRISPR-Cas9 system to generate knockout mice in FVB strain. We designed and synthesized single guide RNA (sgRNA) of CRISPR system for targeting gene, Abtb2. Mouse zygote were obtained from superovulated FVB female mice at 8-10 weeks of age. The sgRNA was injected into pronuclear of the mouse zygote with recombinant Cas9 protein. The microinjected zygotes were cultured for an additional day and only cleaved embryos were selected. The selected embryos were surgically transferred to oviduct of surrogate mother and offsprings were obtained. Genomic DNA were isolated from the offsprings and the target sequence was amplified using PCR. In T7E1 assay, 46.7% among the offsprings were founded as mutants. The PCR products were purified and sequences were analyzed. Most of the mutations were founded as deletion of few sequences at the target site, however, not identical among the each offspring. In conclusion, we found that CRISPR system is very efficient to generate knockout mice in FVB strain.

The interleukin-4 (IL-4) signaling cascade has been identified as a potentially important pathway in the development of allergies. The principal objective of this study was to produce novel transgenic (Tg) mice harboring the luciferase gene under the control of the human IL-4 promoter and the enhancer of IL-4 (CNS-1), in an effort to evaluate three types of allergens including a respiratory sensitizer, vaccine additives, and crude extracts of natural allergens in vivo. A new lineage of Tg mice was generated by the microinjection of pIL-4/Luc/CNS-1 constructs into a fertilized mice egg. The luciferase activity was successfully regulated by the IL-4 promoter in splenocytes cultured from IL-4/Luc/CNS-1 Tg mice. From the first five founder lines, one (#57) evidencing a profound response to ovalbumin was selected for use in evaluating the allergens. Additionally, the lungs, thymus, and lymph nodes of IL-4/Luc/CNS-1 Tg mice evidenced high luciferase activity in response to allergens such as phthalic anhydride (PA), trimellitic anhydride, ovalbumin, gelatin, Dermatophagoides pteronyssinus extracts, and Japanese cedar pollen, whereas key allergy-related indicators including ear thickness, Immunoglobulin E concentration, and the infiltration of inflammatory leukocytes in response to PA were unaltered in the Tg mice relative to the non-Tg mice. Furthermore, the expression levels of endogenous type 2 helper T cells cytokines and proinflammatory cytokines were similarly increased in these organs of IL-4/Luc/CNS-1 Tg mice in response to allergens. These results indicate that IL-4/Luc/CNS-1 Tg mice may be used as an animal model for the evaluation and prediction of the human body response to a variety of allergens originating from the environment and from certain industrial products.

In contrast to the Deuteronomist, the Chronicler places great value on presenting the reforms carried out by Ezechias/Hezekiah. The present study examines the reasons for this and attempts to locate the Chronicler's work historically and theologically from this perspective.

A Korean-Japanese-Chinese aligned wordnet, “CoreNet” is introduced. For the purpose of this paper, the term “wordnet” refers to a network of words. It is constructed based on a shared semantic hierarchy that is originated from NTT Goidaikei (Lexical Hierarchical System). Korean wordnet was constructed through the semantic category assignment to every meaning of Korean words in a dictionary. Verbs and adjectives’ word senses are assigned to the same semantic hierarchy as that of nouns. Each sense of verbs is investigated from corpora for their usage, and compared with Japanese translation. Chinese wordnet with the same semantic hierarchy was built up based on the comparison with Korean wordnet. Each sense of Chinese verb corresponds to Korean with its argument structure. The use of the same semantic hierarchy for nouns and predicates has several advantages. First, the surface forms of nouns and predicates share the similar one, especially in Chinese words. In case of Korean and Japanese, the typical formation is like “do+Noun” in English like “Noun+suru” in Japanese and “Noun+hada” in Korean. Second, the language generation from conceptual structures takes freedom to choose the surface form whether it chooses noun phrases or verb phrases. CoreNet has been constructed by the following principles: word sense mapping to concept, corpus-based, multi-lingualism, and single concept system for multi-languages. The overall flow of construction is based on dictionary-based bootstrapping, incremental similarity-based classification and manual post-editing. Among consideration points, the followings are introduced: multiple concept mapping, verbal noun, and concept splitting. For multiple concept mapping, a word is mapped into numerous concepts that comprise respective meanings of the word. For example, school is an “institution for the instruction of students.” The word school is mapped into three concepts such as location, organization, and facility. For verbal noun, a word that is a verb is assigned to concepts after it is transformed to a noun. For example, “write” is transformed to its noun form “writing” that is mapped into a concept writing falling under event. For concept splitting, every time inconsistency among nodes of concepts is discovered, a node may be added. What differs between CoreNet and NTT Goidaikei is that CoreNet features mapping between word senses (not just words) and concepts. These works have lasted since 1994.

In terminology, the predominance of nouns is an incontestable phenomenon. In Korean terminologies, this predominance of nouns is even more notable because the meaning and function associated with adjectives in Indo-European languages are often realized in noun form. However, the rarer adjectival terms are, the more they are used in restrictive, repetitive ways in specialized domains. Thus, it is important to distinguish the different senses of these terms. In this work, focusing on semantic characterization in terminology, we distinguish the different senses of adjectival medical terms by applying lexico-semantic criteria (L’Homme 2004a) and by classifying the arguments of the adjective into semantic categories (Bae et al. 2002). With this work, we aim to enrich terminological descriptions found in Korean medical dictionnaries by demonstrating empirically a method for distinguishing the different senses of adjectival medical terms. To achieve our goal, we used the KAIST corpus, composed of medical texts (1,500,000 eojeols), and a group of texts on various subjects (40,000,000 eojeols).