Anti-Amyloidogenic and Anti-Apoptotic Role of Melatonin in Alzheimer Disease

Alzheimer disease (AD) is an age-related neurodegenerative disorder characterized by the presence of senile plaques, neurofibrillary tangles and neuronal loss. Amyloid-β protein (Aβ) deposition plays a critical role in the development of AD. It is now generally accepted that massive neuronal death due to apoptosis is a common characteristic in the brains of patients suffering from neurodegenerative diseases, and apoptotic cell death has been found in neurons and glial cells in AD. Melatonin is a secretory product of the pineal gland; melatonin is a potent antioxidant and free radical scavenger and may play an important role in aging and AD. Melatonin decreases during aging and patients with AD have a more profound reduction of this indoleamine. Additionally, the antioxidant properties, the anti-amyloidogenic properties and anti-apoptotic properties of melatonin in AD models have been studied. In this article, we review the anti-amyloidogenic and anti-apoptotic role of melatonin in A

Instance Needs More Care: Rewriting Prompts for Instances Yields Better Zero-Shot Performance

Enabling large language models (LLMs) to perform tasks in zero-shot has been an appealing goal owing to its labor-saving (i.e., requiring no task-specific annotations); as such, zero-shot prompting approaches also enjoy better task generalizability. To improve LLMs' zero-shot performance, prior work has focused on devising more effective task instructions (e.g., ``let's think step by step'' ). However, we argue that, in order for an LLM to solve them correctly in zero-shot, individual test instances need more carefully designed and customized instructions. To this end, we propose PRoMPTd, an approach that rewrites the task prompt for each individual test input to be more specific, unambiguous, and complete, so as to provide better guidance to the task LLM. We evaluated PRoMPTd on eight datasets covering tasks including arithmetics, logical reasoning, and code generation, using GPT-4 as the task LLM. Notably, PRoMPTd achieves an absolute improvement of around 10% on the complex MATH dataset and 5% on the code generation task on HumanEval, outperforming conventional zero-shot methods. In addition, we also showed that the rewritten prompt can provide better interpretability of how the LLM resolves each test instance, which can potentially be leveraged as a defense mechanism against adversarial prompting. The source code and dataset can be obtained from https://github.com/salokr/PRoMPTdComment: Work in progres

Wnt1-Cre-mediated deletion of AP-2α causes multiple neural crest-related defects

AbstractThe AP-2α transcription factor is required for multiple aspects of vertebrate development and mice lacking the AP-2α gene (tcfap2a) die at birth from severe defects affecting the head and trunk. Several of the defects associated with the tcfap2a-null mutation affect neural crest cell (NCC) derivatives including the craniofacial skeleton, cranial ganglia, and heart outflow tract. Consequently, there is considerable interest in the role of AP-2α in neural crest cell function in development and evolution. In addition, the expression of the AP-2α gene is utilized as a marker for premigratory and migratory neural crest cells in many vertebrate species. Here, we have specifically addressed how the presence of AP-2α in neural crest cells affects development by creating a conditional (floxed) version of tcfap2a which has subsequently been intercrossed with mice expressing Cre recombinase under the control of Wnt1 cis-regulatory sequences. Neural crest-specific disruption of tcfap2a results in frequent perinatal lethality associated with neural tube closure defects and cleft secondary palate. A small but significant fraction of mutant mice can survive into adulthood, but have retarded craniofacial growth, abnormal middle ear development, and defects in pigmentation. The phenotypes obtained confirm that AP-2α directs important aspects of neural crest cell function. At the same time, we did not observe several neurocristopathies affecting the head and heart that might be expected based on the phenotype of the AP-2α-null mouse. These results have important implications for the evolution and function of the AP-2 gene family in both the neural crest and the vertebrate embryo

Phylogeny of the genus Morus (Urticales: Moraceae) inferred from ITS and trnL-F sequences

Both nuclear ribosomal ITS and chloroplast trnL-F sequences were acquired from 13 mulberry genotypes belonging to nine species and three varieties, and one paper mulberry. The later belongs to genus B. papyrifera, designed as outgroup, and were analyzed. Within the genus Morus, the sequence diversity of ITS was much higher than that of trnL-F. The results of phylogenetic analyses based on these data (separately or combined) show that the genus Morus is monophyletic group. Strict consensus tree obtained through the Neighbor-joining method can be divided into five major clades in the genus Morus, according to combined sequence data. M. bombycis, M. alba var. venose formed clades A and B, respectively. Clade C comprises of 5 species; M. rotundiloba, M. atropurpurea, M. mongolica, M. australi, and M. mongolica var. diabolica. Clade D comprises of 3 species; M. wittiorum, M. laevigata, and M. alba. Clade E comprises of 2 species; M. multicaulis, and M.alba var. macrophylla. The results from cluster analysis were basically in agreement with the existing morphologic classification.African Journal of Biotechnology Vol. 4 (6), pp. 563-569, 200

Optimum Design for Mechanical Structures and Material Properties of the Dual-Elbow-Bar Mechanism

According to the kinematic equation of the die-cutting machine with the dual-elbow-bar mechanism, the angular acceleration curve figure can be obtained exactly through the analysis of MATLAB program when the die-cutting machine runs at the highest speed (6000 r/h). The material properties of the cam driving mechanism are analyzed by QFD (Quality Function Deployment) method, and the optimum design project is presented based on conjugate cam driving mechanism. The reverse design and the outline of conjugate cam mechanism are obtained by MATLAB program. The kinematical form of optimized design conjugate cam driving mechanism is simulated and analyzed by ADAMS software. The results show that the optimum design mechanism could raise the highest speed of the die-cutting machine up to 7500 r/h and improve the overall performance of the machine

Comparison of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assessment for Her-2 status in breast cancer

<p>Abstract</p> <p>Background</p> <p>The concordance rate between IHC and FISH according to clinical performance is still controversial. We report a prospective study to reflect the concordance between IHC and FISH in Guilin city, People's Republic of China.</p> <p>Methods</p> <p>Fifty cases of invasive ductal carcinoma of breast tested by IHC and scored as 0, 1+, 2+ and 3+ by pathologists were further analyzed by FISH using a commercially available double-color probe, and the FISH findings were compared with IHC test results.</p> <p>Results</p> <p>A total concordance of 82.0% was observed with a Kappa coefficient of 0.640 (P < 0.001). A high discordance was observed in 30.0% of the patients with IHC 2+, 7.1% in IHC 3+, 19.2% overall in IHC 0 and 1+.</p> <p>Conclusion</p> <p>The IHC can be used firstly to screen the HER-2 status, and FISH can be used as a supplementary role to IHC and 2+ and some negative cases. And only those cases with Her-2 status of IHC 3+ or FISH positive should be treated with Herceptin.</p