Global analysis of serine/threonine and tyrosine protein phosphatase catalytic subunit genes in Neurospora crassa reveals interplay between phosphatases and the p38 mitogen-activated protein kinase.

Protein phosphatases are integral components of the cellular signaling machinery in eukaryotes, regulating diverse aspects of growth and development. The genome of the filamentous fungus and model organism Neurospora crassa encodes catalytic subunits for 30 protein phosphatase genes. In this study, we have characterized 24 viable N. crassa phosphatase catalytic subunit knockout mutants for phenotypes during growth, asexual development, and sexual development. We found that 91% of the mutants had defects in at least one of these traits, whereas 29% possessed phenotypes in all three. Chemical sensitivity screens were conducted to reveal additional phenotypes for the mutants. This resulted in the identification of at least one chemical sensitivity phenotype for 17 phosphatase knockout mutants, including novel chemical sensitivities for two phosphatase mutants lacking a growth or developmental phenotype. Hence, chemical sensitivity or growth/developmental phenotype was observed for all 24 viable mutants. We investigated p38 mitogen-activated protein kinase (MAPK) phosphorylation profiles in the phosphatase mutants and identified nine potential candidates for regulators of the p38 MAPK. We demonstrated that the PP2C class phosphatase pph-8 (NCU04600) is an important regulator of female sexual development in N. crassa. In addition, we showed that the Δcsp-6 (ΔNCU08380) mutant exhibits a phenotype similar to the previously identified conidial separation mutants, Δcsp-1 and Δcsp-2, that lack transcription factors important for regulation of conidiation and the circadian clock

Mapping the mammalian ribosome quality control complex interactome using proximity labeling approaches.

Previous genetic and biochemical studies from Saccharomyces cerevisiae have identified a critical ribosome-associated quality control complex (RQC) that facilitates resolution of stalled ribosomal complexes. While components of the mammalian RQC have been examined in vitro, a systematic characterization of RQC protein interactions in mammalian cells has yet to be described. Here we utilize both proximity-labeling proteomic approaches, BioID and APEX, and traditional affinity-based strategies to both identify interacting proteins of mammalian RQC members and putative substrates for the RQC resident E3 ligase, Ltn1. Surprisingly, validation studies revealed that a subset of substrates are ubiquitylated by Ltn1 in a regulatory manner that does not result in subsequent substrate degradation. We demonstrate that Ltn1 catalyzes the regulatory ubiquitylation of ribosomal protein S6 kinase 1 and 2 (RPS6KA1, RPS6KA3). Further, loss of Ltn1 function results in hyperactivation of RSK1/2 signaling without impacting RSK1/2 protein turnover. These results suggest that Ltn1-mediated RSK1/2 ubiquitylation is inhibitory and establishes a new role for Ltn1 in regulating mitogen-activated kinase signaling via regulatory RSK1/2 ubiquitylation. Taken together, our results suggest that mammalian RQC interactions are difficult to observe and may be more transient than the homologous complex in S. cerevisiae and that Ltn1 has RQC-independent functions

Cerita rakyat daerah sulawesi tenggara

Buku ini berisi tentang cerita rakyat di daerah sulawesi tenggara dari berbagai kabupaten. Berhubung belum begitu banyak dikenal daerah ini dari dahulu bahkan sampai sekarang ini maka dalam rangka penulisan dan pencatatan Cerita Rakyat di daerah ini rasanya perlu menge-mukakan beberapa aspek tertentu yang bersangkut paut dengan keadaan daerah dan penduduknya, mata pencahariannya, potensi ekonominya, agama dan kepercayaannya dan situasi masyarakat dalam masa pembangunan dewasa ini

Sleepiness and cognition in young adults who gamble and use alcohol

Abstract Background and aims Past research suggests that sleep problems are associated with increased risky decision-making. Similarly, gambling disorder and alcohol use disorder are also associated with increased risky decision-making. Individuals with gambling disorder or alcohol use disorder have also reported higher rates of sleep problems compared to normal healthy controls. As such, we sought to examine whether sleep problems play a role in the development of alcohol use disorder or gambling disorder. Methods One hundred and forty-one individuals who gamble and use alcohol, yet do not meet criteria for gambling disorder or alcohol use disorder, were assessed to determine the correlation between sleepiness, amount of sleep obtained, decision-making, and alcohol or gambling behaviors. Results Our results suggest that inconsistent sleep patterns may be associated with increased frequency of alcohol use and gambling. We did not, however, find a significant correlation between sleep factors and decision-making. Discussion Further research is needed to examine the specific relationship between sleep patterns and alcohol use and gambling frequency. Overall these data suggest that sleepiness or sleep and risky decision-making is not a significant factor in gambling and alcohol use behaviors in individuals not meeting criteria for alcohol use disorder or gambling disorder

THE BEHAVIORAL EFFECTS OF FIRST-GENERATION ELECTRONIC CIGARETTES AFTER 24-HOUR TOBACCO DEPRIVATION

Little is currently known about the ability of electronic cigarettes to manage tobacco withdrawal symptoms and their abuse liability. In the current study eight conventional cigarette smokers completed nine within-subject study sessions. In the first session participants practiced using an electronic cigarette containing 16 mg/ml of nicotine over six 10-puff bouts. Remaining study sessions were comprised of four two-day blocks (one for each condition), which assessed measures of tobacco withdrawal symptoms and abuse liability following unrestricted cigarette smoking and 24-hour tobacco deprivation. Study conditions included an electronic cigarette with 0, 8, or 16 mg/ml nicotine concentrations, or preferred brand of conventional cigarette. Following 24-hours of tobacco deprivation, smoking conventional cigarettes ameliorated many of the self-report and physiological symptoms (decreased heart rate) associated with tobacco deprivation, while no attenuation of withdrawal symptoms was indicated following using electronic cigarettes, independent of nicotine dose. On abuse liability measures there were no significant changes following using an electronic cigarette (regardless of nicotine concentration), while conventional cigarettes engendered significant changes on abuse liability measures. Within the conditions of this study, first-generation electronic cigarettes had no measurable efficacy in ameliorating tobacco withdrawal symptoms and a reduced abuse liability compared to conventional tobacco cigarettes

THE SELF-REPORTED AND BEHAVIORAL EFFECTS OF PROPYLENE GLYCOL AND VEGETABLE GLYCERIN IN ELECTRONIC CIGARETTE LIQUIDS

Little is known about how electronic cigarette (EC) users manipulate device parameters, what factors drive their use, and how non-nicotine ingredients influence the stimulus effects of EC aerosols. The ingredients propylene glycol (PG) or vegetable glycerin (VG) serve as the base for virtually all electronic cigarette liquids, and information on how they affect the using experience would provide important groundwork for the study of other ingredients. In this dissertation, results from a survey and laboratory study focused on the stimulus effects of ECs, and the influence of PG and VG, will be discussed. A total of 522 regular EC users completed a survey comprised of an electronic cigarette dependence questionnaire, questions on tobacco and electronic cigarette use, and device and liquid preferences. This was followed by a laboratory study with sixteen electronic cigarette users completing five test days (one practice and four assessment days). In the laboratory study, following one hour of nicotine deprivation, two sampling puffs from liquid formulations containing 100/0, 75/25, 50/50, 25/75, and 0/100% PG/VG concentrations were administered in random order during five assessments, each separated by 20 min. Primary outcome measures were self-reported stimulus characteristics and breakpoint on a multiple-choice procedure. Survey results indicated that ability to change device voltage, and level of resistance, was significantly associated with level of nicotine dependence, as was amount of liquid consumed, nicotine concentration, and milligrams of nicotine used per week. Participants also rated \u27good taste\u27 as the most important consideration when purchasing and using liquids, and PG was associated with undesirable effects and VG with desirable effects. Laboratory results indicated that greater VG content was associated with greater reports of visibility of the exhalant (i.e. “cloud”). Liquids with mixtures of PG or VG were associated with conventional cigarette smoking sensations and greater reductions of systolic blood pressure compared to formulations with only PG or VG. There was no significant effect of liquid formulation on the multiple-choice procedure, but puffs were rarely chosen over even the smallest monetary option ($0.05), suggesting minimal reinforcing efficacy. In conclusion, survey data indicate that a wide range device parameter settings and liquid ingredients are preferred by daily e-cigarette users, and that individuals with greater nicotine dependence favor voltage control devices, and lower resistance heating elements. Survey data also indicated that taste is a key factor for EC liquid selection, and relative concentrations of propylene glycol and vegetable glycerin may have a significant impact on the reinforcing effects of liquids. In contrast, laboratory data suggests that PG or VG do not significantly impact the abuse liability of EC liquids, though reinforcing effects of these ingredients was unclear in the laboratory study

Dynamics of learning among pre-primary school learners in Uyo Senatorial District, Nigeria: an exploration of formal and informal education processes.

Doctoral Degree. University of KwaZulu-Natal, Durban.The concept ‘Early Childhood Education’ (ECE) or pre-primary education as it known in Nigeria is referred to as Early Childhood Care and Education (ECCE) in the Republic of China. It is also called Early Childhood Development in Tanzania and South Africa. In the United States of America, this phase of education is known as ECE. In spite of the many different names given to this level of education by different countries, this is the kind of education which children between the ages of three and five receive. Therefore, the focus of this study was to explore the dynamics that surround the way pre-primary school learners learn in formal and informal education settings. In specific terms, the purpose of this study was to provide an in-depth description on the forces that impact learning of young children between the ages of three and five both at school and home. By engaging in research into the learning among pre-primary school learners, I shed some light on the dynamics that impact ways in which children learn both at school and home. In the light of the above this study therefore seeks to achieve the following objectives: to examine the language pre-primary school learners adopt for learning; to examine the impact of language on pre-primary school learners’ learning; and to understand the dynamics that surround the way pre-primary school learners learn in formal and informal education settings. Based on the research objectives stated above, three key research questions were developed to guide the study. The questions are: what language do pre-primary school learners adopt for learning? How does language impact pre-primary school learners’ learning? What are the dynamics that surround the way pre-primary school learners learn in formal and informal education settings? Based on the nature of the study which bordered on the social phenomena, a qualitative approach was adopted. In line with this approach, an interpretive paradigm was adopted in order to make sense of and to have an in-depth understanding of the dynamics that surround ways in which pre-primary school learners learn in formal and informal education settings. Individual and focus group interviews were designed and administered to 15 teachers and 8 parents from three schools. The transcribed data was subjected to an open coding and the emerging themes were subjected to thematic analysis. From the findings, it was discovered that the language of the immediate community, the mother and English language were the languages used in the teaching of the children in formal and informal settings. In line with the second question, it was indicated that identification, presentation, discussion of objects, development of literacy skills, and promoting communication had a possible impact on language in pre-primary school learners’ learning. In addition, the dynamics that influenced ways children learned were through playing, imitation, story-telling and folktales, and drawing enhanced by children’s readiness to learn, children’s willingness to learn, children’s maturity, availability of instructional resources, and parents’/teachers’ attitude towards children . One of the recommendations was that children who come from ethnic group different from where the school is located, and who want to attend pre-primary school in area, should first and foremost, be subjected to six months training in the language of immediate community or mother tongue and that subjecting the children to six months language familiarisation will assist them to adjust immediately in the class as well as ensuring uniformity of language in the classroom

An Improved Differential Evolution Algorithm for Numerical Optimization Problems

The differential evolution algorithm has gained popularity for solving complex optimization problems because of its simplicity and efficiency. However, it has several drawbacks, such as a slow convergence rate, high sensitivity to the values of control parameters, and the ease of getting trapped in local optima. In order to overcome these drawbacks, this paper integrates three novel strategies into the original differential evolution. First, a population improvement strategy based on a multi-level sampling mechanism is used to accelerate convergence and increase the diversity of the population. Second, a new self-adaptive mutation strategy balances the exploration and exploitation abilities of the algorithm by dynamically determining an appropriate value of the mutation parameters; this improves the search ability and helps the algorithm escape from local optima when it gets stuck. Third, a new selection strategy guides the search to avoid local optima. Twelve benchmark functions of different characteristics are used to validate the performance of the proposed algorithm. The experimental results show that the proposed algorithm performs significantly better than the original DE in terms of the ability to locate the global optimum, convergence speed, and scalability. In addition, the proposed algorithm is able to find the global optimal solutions on 8 out of 12 benchmark functions, while 7 other well-established metaheuristic algorithms, namely NBOLDE, ODE, DE, SaDE, JADE, PSO, and GA, can obtain only 6, 2, 1, 1, 1, 1, and 1 functions, respectively. Doi: 10.28991/HIJ-2023-04-02-014 Full Text: PD