Gender Differences in Cognition among Older Adults in China

In this paper, the authors model gender differences in cognitive ability in China using a new sample of middle-aged and older Chinese respondents. Modeled after the American Health and Retirement Survey (HRS), the CHARLS Pilot survey respondents are 45 years and older in two quite distinct provinces—Zhejiang a high growth industrialized province on the East Coast, and Gansu, a largely agricultural and poor Province in the West. Their measures of cognition in CHARLS relies on two measures that proxy for different dimensions of adult cognition—episodic memory and intact mental status. They relate both these childhood health measures to adult health and SES outcomes during the adult years. They find large cognitive differences to the detriment of women that were mitigated by large gender differences in education among these generations of Chinese people. These gender differences in cognition are especially concentrated within poorer communities in China with gender difference being more sensitive to community level attributes than to family level attributes, with economic resources. In traditional poor Chinese communities, there are strong economic incentives to favor boys at the expense of girls not only in their education outcomes, but in their nutrition and eventually their adult height. These gender cognitive differences have been steadily decreasing across birth cohorts as the economy of China grew rapidly. Among younger cohorts of young adults in China, there is no longer any gender disparity in cognitive ability.

HoxA9 binds and represses the Cebpa +8 kb enhancer

C/EBPα plays a key role in specifying myeloid lineage development. HoxA9 is expressed in myeloid progenitors, with its level diminishing during myeloid maturation, and HOXA9 is over-expressed in a majority of acute myeloid leukemia cases, including those expressing NUP98-HOXD13. The objective of this study was to determine whether HoxA9 directly represses Cebpa gene expression. We find 4-fold increased HoxA9 and 5-fold reduced Cebpa in marrow common myeloid and LSK progenitors from Vav-NUP98-HOXD13 transgenic mice. Conversely, HoxA9 decreases 5-fold while Cebpa increases during granulocytic differentiation of 32Dcl3 myeloid cells. Activation of exogenous HoxA9-ER in 32Dcl3 cells reduces Cebpa mRNA even in the presence of cycloheximide, suggesting direct repression. Cebpa transcription in murine myeloid cells is regulated by a hematopoietic-specific +37 kb enhancer and by a more widely active +8 kb enhancer. ChIP-Seq analysis of primary myeloid progenitor cells expressing exogenous HoxA9 or HoxA9-ER demonstrates that HoxA9 localizes to both the +8 kb and +37 kb Cebpa enhancers. Gel shift analysis demonstrates HoxA9 binding to three consensus sites in the +8 kb enhancer, but no affinity for the single near-consensus site present in the +37 kb enhancer. Activity of a Cebpa +8 kb enhancer/promoter-luciferase reporter in 32Dcl3 or MOLM14 myeloid cells is increased ~2-fold by mutation of its three HOXA9-binding sites, suggesting that endogenous HoxA9 represses +8 kb Cebpa enhancer activity. In contrast, mutation of five C/EBPα-binding sites in the +8 kb enhancer reduces activity 3-fold. Finally, expression of a +37 kb enhancer/promoter-hCD4 transgene reporter is reduced ~2-fold in marrow common myeloid progenitors when the Vav-NUP98-HOXD13 transgene is introduced. Overall, these data support the conclusion that HoxA9 represses Cebpa expression, at least in part via inhibition of its +8 kb enhancer, potentially allowing normal myeloid progenitors to maintain immaturity and contributing to the pathogenesis of acute myeloid leukemia associated with increased HOXA9

MLCopilot: Unleashing the Power of Large Language Models in Solving Machine Learning Tasks

The field of machine learning (ML) has gained widespread adoption, leading to a significant demand for adapting ML to specific scenarios, which is yet expensive and non-trivial. The predominant approaches towards the automation of solving ML tasks (e.g., AutoML) are often time consuming and hard to understand for human developers. In contrast, though human engineers have the incredible ability to understand tasks and reason about solutions, their experience and knowledge are often sparse and difficult to utilize by quantitative approaches. In this paper, we aim to bridge the gap between machine intelligence and human knowledge by introducing a novel framework MLCopilot, which leverages the state-of-the-art LLMs to develop ML solutions for novel tasks. We showcase the possibility of extending the capability of LLMs to comprehend structured inputs and perform thorough reasoning for solving novel ML tasks. And we find that, after some dedicated design, the LLM can (i) observe from the existing experiences of ML tasks and (ii) reason effectively to deliver promising results for new tasks. The solution generated can be used directly to achieve high levels of competitiveness

Proteome of the central apparatus of a ciliary axoneme

Nearly all motile cilia have a 9+2 axoneme containing a central apparatus (CA), consisting of two central microtubules with projections, that is essential for motility. To date, only 22 proteins are known to be CA components. To identify new candidate CA proteins, we used mass spectrometry to compare axonemes of wild-type Chlamydomonas and a CA-less mutant. We identified 44 novel candidate CA proteins, of which 13 are conserved in humans. Five of the latter were studied more closely, and all five localized to the CA; therefore, most of the other candidates are likely to also be CA components. Our results reveal that the CA is far more compositionally complex than previously recognized and provide a greatly expanded knowledge base for studies to understand the architecture of the CA and how it functions. The discovery of the new conserved CA proteins will facilitate genetic screening to identify patients with a form of primary ciliary dyskinesia that has been difficult to diagnose

Cloning, reassembling and integration of the entire nikkomycin biosynthetic gene cluster into Streptomyces ansochromogenes lead to an improved nikkomycin production

<p>Abstract</p> <p>Background</p> <p>Nikkomycins are a group of peptidyl nucleoside antibiotics produced by <it>Streptomyces ansochromogenes</it>. They are competitive inhibitors of chitin synthase and show potent fungicidal, insecticidal, and acaricidal activities. Nikkomycin X and Z are the main components produced by <it>S. ansochromogenes</it>. Generation of a high-producing strain is crucial to scale up nikkomycins production for further clinical trials.</p> <p>Results</p> <p>To increase the yields of nikkomycins, an additional copy of nikkomycin biosynthetic gene cluster (35 kb) was introduced into nikkomycin producing strain, <it>S. ansochromogenes </it>7100. The gene cluster was first reassembled into an integrative plasmid by Red/ET technology combining with classic cloning methods and then the resulting plasmid(pNIK)was introduced into <it>S. ansochromogenes </it>by conjugal transfer. Introduction of pNIK led to enhanced production of nikkomycins (880 mg L^-1, 4 -fold nikkomycin X and 210 mg L^-1, 1.8-fold nikkomycin Z) in the resulting exconjugants comparing with the parent strain (220 mg L^-1nikkomycin X and 120 mg L^-1nikkomycin Z). The exconjugants are genetically stable in the absence of antibiotic resistance selection pressure.</p> <p>Conclusion</p> <p>A high nikkomycins producing strain (1100 mg L^-1nikkomycins) was obtained by introduction of an extra nikkomycin biosynthetic gene cluster into the genome of <it>S. ansochromogenes</it>. The strategies presented here could be applicable to other bacteria to improve the yields of secondary metabolites.</p

Evaluation System of High-quality Development of Cities in the Yangtze River Economic Belt under the New Development Pattern

In view of the high-quality development of cities in the Yangtze River Economic Belt, and in combination with the characteristics of the new development pattern, this paper constructs the evaluation index system of high-quality development of cities in the Yangtze River Economic Belt from five aspects which contain innovative development, coordinated development, green development, open development, and shared development. Firstly, this paper constructs the evaluation model of the high-quality development of the cities in the Yangtze River Economic Belt. Secondly, the paper uses the analytic hierarchy process to determine the weight of the indicators. Thirdly, the paper uses the fuzzy comprehensive evaluation method to establish the evaluation set of the indicators. Finally, it concludes that the high-quality development level of the cities in the Yangtze River Economic Belt is at the middle level

Selectively improving nikkomycin Z production by blocking the imidazolone biosynthetic pathway of nikkomycin X and uracil feeding in Streptomyces ansochromogenes

<p>Abstract</p> <p>Background</p> <p>Nikkomycins are a group of peptidyl nucleoside antibiotics and act as potent inhibitors of chitin synthases in fungi and insects. Nikkomycin X and Z are the main components produced by <it>Streptomyces ansochromogenes</it>. Of them, nikkomycin Z is a promising antifungal agent with clinical significance. Since highly structural similarities between nikkomycin Z and X, separation of nikkomycin Z from the culture medium of <it>S. ansochromogenes </it>is difficult. Thus, generating a nikkomycin Z selectively producing strain is vital to scale up the nikkomycin Z yields for clinical trials.</p> <p>Results</p> <p>A nikkomycin Z producing strain (sanPDM) was constructed by blocking the imidazolone biosynthetic pathway of nikkomycin X via genetic manipulation and yielded 300 mg/L nikkomycin Z and abolished the nikkomycin X production. To further increase the yield of nikkomycin Z, the effects of different precursors on its production were investigated. Precursors of nucleoside moiety (uracil or uridine) had a stimulatory effect on nikkomycin Z production while precursors of peptidyl moiety (L-lysine and L-glutamate) had no effect. sanPDM produced the maximum yields of nikkomycin Z (800 mg/L) in the presence of uracil at the concentration of 2 g/L and it was approximately 2.6-fold higher than that of the parent strain.</p> <p>Conclusion</p> <p>A high nikkomycin Z selectively producing was obtained by genetic manipulation combined with precursors feeding. The strategy presented here might be applicable in other bacteria to selectively produce targeted antibiotics.</p