scholarly journals Hexosamine pathway activation improves memory but does not extend lifespan in mice.

2022 ◽  
Author(s):  
Kira Allmeroth ◽  
Matías D Hartman ◽  
Martin Purrio ◽  
Andrea Mesaros ◽  
Martin Sebastian Denzel
Keyword(s):  
Protein Quality ◽  
Young Male ◽  
Young Female ◽  
Mutant Form ◽  
Long Term Effects ◽  
Potential Health ◽  
Hexosamine Biosynthetic Pathway ◽  
Hexosamine Pathway ◽  
Mouse Tissues ◽  
Key Enzyme

Glucosamine feeding and genetic activation of the hexosamine biosynthetic pathway (HBP) have been linked to improved protein quality control and lifespan extension in various species. Thus, there is considerable interest in the potential health benefits of dietary supplementation with glucosamine or other HBP metabolites in people. The HBP is a sensor for energy availability and its activation has been implicated in tumor progression and diabetes in higher organisms. As the activation of the HBP has been linked to longevity in lower animals, it is imperative to explore the long-term effects of chronic HBP activation in mammals, which has not been examined so far. To address this issue, we activated the HBP in mice both genetically and through metabolite supplementation, and evaluated metabolism, memory, and survival. GlcNAc supplementation in the drinking water had no adverse effect on weight gain in males but increased weight in young female mice. Glucose or insulin tolerance were not affected up to 20 months of age. Of note, we observed improved memory in the Morris water maze in young male mice supplemented with GlcNAc. Survival was not changed by GlcNAc supplementation. To assess the effects of genetic HBP activation we overexpressed the key enzyme GFAT1 as well as a constitutively activated mutant form in all mouse tissues. We detected elevated UDP-GlcNAc levels in mouse brains, but did not find any effects on behavior, memory, or survival. Together, while dietary GlcNAc supplementation did not extend survival in mice, it positively affected memory and is generally well tolerated.

scholarly journals Bop1 Is a Mouse WD40 Repeat Nucleolar Protein Involved in 28S and 5.8S rRNA Processing and 60S Ribosome Biogenesis

2000 ◽  
Vol 20 (15) ◽  
pp. 5516-5528 ◽  
Author(s):  
Žaklina Strezoska ◽  
Dimitri G. Pestov ◽  
Lester F. Lau
Keyword(s):  
Ribosome Biogenesis ◽  
Ribosomal Subunit ◽  
Weight Fraction ◽  
Rnase A ◽  
Mutant Form ◽  
Rrna Processing ◽  
Ribonucleoprotein Complexes ◽  
Nuclear Extracts ◽  
Mouse Tissues ◽  
Mouse Cells

ABSTRACT We have identified and characterized a novel mouse protein, Bop1, which contains WD40 repeats and is highly conserved through evolution. bop1 is ubiquitously expressed in all mouse tissues examined and is upregulated during mid-G1 in serum-stimulated fibroblasts. Immunofluorescence analysis shows that Bop1 is localized predominantly to the nucleolus. In sucrose density gradients, Bop1 from nuclear extracts cosediments with the 50S-80S ribonucleoprotein particles that contain the 32S rRNA precursor. RNase A treatment disrupts these particles and releases Bop1 into a low-molecular-weight fraction. A mutant form of Bop1, Bop1Δ, which lacks 231 amino acids in the N- terminus, is colocalized with wild-type Bop1 in the nucleolus and in ribonucleoprotein complexes. Expression of Bop1Δ leads to cell growth arrest in the G1phase and results in a specific inhibition of the synthesis of the 28S and 5.8S rRNAs without affecting 18S rRNA formation. Pulse-chase analyses show that Bop1Δ expression results in a partial inhibition in the conversion of the 36S to the 32S pre-rRNA and a complete inhibition of the processing of the 32S pre-rRNA to form the mature 28S and 5.8S rRNAs. Concomitant with these defects in rRNA processing, expression of Bop1Δ in mouse cells leads to a deficit in the cytosolic 60S ribosomal subunits. These studies thus identify Bop1 as a novel, nonribosomal mammalian protein that plays a key role in the formation of the mature 28S and 5.8S rRNAs and in the biogenesis of the 60S ribosomal subunit.

scholarly journals Young female doctors report achieving fewer surgical skills than young male doctors

BMJ ◽  
1996 ◽  
Vol 313 (7062) ◽  
pp. 944-944 ◽  
Author(s):  
G. Falck ◽  
G. Brattebo
Keyword(s):  
Young Male ◽  
Young Female ◽  
Surgical Skills

Health Potential for Functional Green Teas?

2008 ◽  
Vol 78 (6) ◽  
pp. 275-281 ◽  
Author(s):  
Niels Boon
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Body Composition ◽  
Energy Metabolism ◽  
Green Tea ◽  
Moderate Physical Activity ◽  
Long Term Effects ◽  
Potential Health ◽  
Major Health Problem ◽  
The Metabolic Syndrome

Obesity is a major health problem in the developed and developing world. Many “functional” foods and ingredients are advocated for their effects on body composition but few have consistent scientific support for their efficacy. However, an increasing amount of mechanistic and clinical evidence is building for green tea. The tea plant is naturally rich in a group of antioxidants known as catechins. Unlike black tea, green tea production involves little processing and fermentation and therefore, green tea brews are rich in catechins. Green tea has been suggested to have a number of potential health benefits in areas such as cardiovascular disease, cancer prevention, glucose homeostasis and dental health. Although there is some promising evidence in all of these areas, more data from human intervention trials are needed. A lot of attention has lately been focused on the beneficial effects of green tea on body composition and particularly visceral fat, which has been shown to have a strong link with different components of the metabolic syndrome such as cardiovascular disease and type 2 diabetes. Most, but not all, of the positive results come from a number Asian studies, in which overweight subjects (men and women) consumed green tea for approximately 12 weeks. Finally, green tea may also have measurable acute effects on energy metabolism and fat oxidation and in particular during physical activity, as evidenced by other studies specifically looking at these endpoints. Small cumulative effects on energy metabolism could also be responsible for the longer-tem effects of green tea on body composition, and these long-term effects may also be most apparent in the context of moderate physical activity. However, more research is needed to further clarify the exact mechanisms of action and to extrapolate these findings to non-Asian populations.

scholarly journals Targeting a critical step in fungal hexosamine biosynthesis

2020 ◽  
Vol 295 (26) ◽  
pp. 8678-8691 ◽  
Author(s):  
Deborah E. A. Lockhart ◽  
Mathew Stanley ◽  
Olawale G. Raimi ◽  
David A. Robinson ◽  
Dominika Boldovjakova ◽  
...  
Keyword(s):  
Cell Wall ◽  
Antifungal Drugs ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Hexosamine Biosynthetic Pathway ◽  
Hexosamine Biosynthesis ◽  
Key Enzyme ◽  
Opportunistic Fungal Pathogen ◽  
Extracellular Environment ◽  
Chemical Evidence

Aspergillus fumigatus is a human opportunistic fungal pathogen whose cell wall protects it from the extracellular environment including host defenses. Chitin, an essential component of the fungal cell wall, is synthesized from UDP-GlcNAc produced in the hexosamine biosynthetic pathway. As this pathway is critical for fungal cell wall integrity, the hexosamine biosynthesis enzymes represent potential targets of antifungal drugs. Here, we provide genetic and chemical evidence that glucosamine 6-phosphate N-acetyltransferase (Gna1), a key enzyme in this pathway, is an exploitable antifungal drug target. GNA1 deletion resulted in loss of fungal viability and disruption of the cell wall, phenotypes that could be rescued by exogenous GlcNAc, the product of the Gna1 enzyme. In a murine model of aspergillosis, the Δgna1 mutant strain exhibited attenuated virulence. Using a fragment-based approach, we discovered a small heterocyclic scaffold that binds proximal to the Gna1 active site and can be optimized to a selective submicromolar binder. Taken together, we have provided genetic, structural, and chemical evidence that Gna1 is an antifungal target in A. fumigatus.

scholarly journals Prevalence of Haemonchus contortus Infections in Sheep and Goats in Nyagatare District, Rwanda

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Borden Mushonga ◽  
Dismas Habumugisha ◽  
Erick Kandiwa ◽  
Oscar Madzingira ◽  
Alaster Samkange ◽  
...  
Keyword(s):  
Haemonchus Contortus ◽  
Small Ruminants ◽  
Young Male ◽  
Young Female ◽  
Gastrointestinal Parasites ◽  
Selective Treatment ◽  
Sheep And Goats ◽  
Viable Solution ◽  
High Prevalence ◽  
Mcmaster Method

This study investigated the overall prevalence of Haemonchus contortus infection in sheep and goats from five purposively selected subdivisions (sectors) of Nyagatare district from January to December 2014, after a high prevalence of gastrointestinal parasites and generalized poor productivity was reported in small ruminants in some districts of Rwanda. Faecal egg counts (FEC) were performed using the Modified Wisconsin Sugar Floatation method and the Fluorescent-labeled peanut-lectin agglutination test while enumerations, as log (FEC), were done using the modified McMaster method. The overall prevalence of H. contortus infection in sheep and goats was 75.7% (n=949). The overall prevalence of H. contortus infection in sheep (83.4%, n=314) was higher than in goats (71.8%, n=635) (Odds Ratio [OR] 1.98, 95% Confidence Interval [CI]: 1.40-2.79, and p≤0.001). The prevalence of H. contortus infection in female goats (74.2%) was higher than in male goats (64.3%) (OR 1.60, 95% CI: 1.09-2.36, and p=0.01). The prevalence of H. contortus infection in goats from Nyagatare was higher than in goats from Matimba (OR 3.25, 95% CI: 1.76-5.99, and p≤0.001) and from Katabagemu (OR 3.67, 95% CI: 2.04-6.59, and p≤0.001). The prevalence of H. contortus infection in goats from Karangazi was higher than in goats from Matimba (OR 4.72, 95% CI: 2.40-9.28, and p≤0.001). The overall mean monthly log (FEC) for H. contortus in sheep and goats were highest in April (18.9±0.2 and 14.05±0.1, respectively) and October (19.25± 0.2 and 13.75±0.1, respectively). Though, overall, sheep in Nyagatare district were at greater risk of H. contortus infection and goats from Nyagatare and Karangazi sectors were paradoxically at greater risk of H. contortus infection. It was also apparent that young female goats were at greater risk of H. contortus infection than young male goats. H. contortus infection is endemic in small ruminants in Nyagatare district and possibly other districts in Rwanda. Targeted selective treatment (TST) using FAMACHA with emphasis on low-lying swampy pastures and appropriate anthelmintic drugs may be the most economically viable solution in the short term. In the long term breeding of H. contortus resistant small ruminants and strategic grazing using the concept of refugia may bring about considerable relief from H. contortus infection in Nyagatare district, in particular, and Rwanda at large.

Modelling of Pedestrian Speed-Density and Volume-Density Relationships in Outdoor Walkways

2015 ◽  
Vol 73 (4) ◽  
Author(s):  
Hashim Mohammed Alhassan ◽  
Nordiana Mashros
Keyword(s):  
Adult Female ◽  
Flow Rate ◽  
Adult Male ◽  
Young Male ◽  
The United States ◽  
Young Female ◽  
Pedestrian Flow ◽  
Flow Parameters ◽  
City District ◽  
The City

The aim of this study was to model pedestrian flow parameters needed in the design of pedestrian facilities. The study also characterized the flow with a view to understanding pedestrian interaction problems especially with regards to their congestion. Twenty-five locations across Kano metropolis were selected for study, thirteen locations from the city district while twelve sites were chosen from the Waje district. All the sites were high flow pedestrian locations that met the study objectives. The data was categorized into four; young male, adult male, young female and adult female. The results indicated that adult women walked faster than their male counterparts in the City district while young males were faster than the female. The adult female recorded an average speed of 73.90 m/min against the speed of 71.30 m/min for the adult male. The average characteristics of the pedestrian in the city district are speed 67.30 m/min; density 11.23 Ped/m2 and volume 33.60 Ped/m/min. In the Waje district, however, the male pedestrian whether adult or young walked faster than their corresponding female counterparts with speed of 71.45 m/min for the adult male and 59.90 m/min for the adult female. The young male was faster than the young female by 17.9%. The average pedestrian flow parameters for the Waje district indicated a combine speed of 60.21 m/min; density of 8.72 Ped/m2 and volume of 30.92 Ped/m/min. The pedestrians in the city district had a higher flow rate, higher density and higher speed than those of the Waje district. This means the city district is a little more concentrated than the Waje district in terms of pedestrian flow. The aggregate average flow parameters of pedestrians in the metropolitan area gave the following parameters: speed 68.92 m/min; density 10.03 Ped/m2 and volume 32.33 Ped/m/min. The predictive models for Kano showed a free flow speed of 59.55 m/min and a maximum flow rate of 73.0 Ped/m/min. Comparing the Kano pedestrian model with other countries it was found that the Kano pedestrian walked slower than pedestrians from Singapore and the United States

Faultlines

2017 ◽  
Author(s):  
Keith Murnighan* ◽  
Dora Lau
Keyword(s):  
Virtual Teams ◽  
Strategic Alliances ◽  
Ad Hoc ◽  
Group Performance ◽  
Young Male ◽  
Young Female ◽  
Top Management Teams ◽  
International Joint Ventures ◽  
Information And Communication ◽  
Communication Challenges

Group faultlines are hypothetical dividing lines that may split a group into subgroups based on one or more attributes. An example of a strong faultline is a group of two young female Asians and two senior male Caucasians. Members’ alignment of age, sex, and ethnicity facilitates the formation of two homogeneous subgroups. On the other hand, when a group consists of a young female Asian, a young male Caucasian, a senior female Caucasian, and a senior male Asian, the group faultline is considered weak because subgroups, regardless of how they are formed, are diverse. As a relatively new form of group compositional pattern, the group faultline is associated with subgroup formation, and these subgroups, rather than the whole group, can easily become the focus of attention. When members strive to obtain more resources and protect their subgroups, between-subgroup conflict, behavioral disintegration, lack of trust, lack of willingness to share information, and communication challenges are likely. As a result, group performance is often negatively affected, and sometimes groups may even be dissolved. These results were repeatedly found in studies of experimental groups, ad-hoc project groups, organizational teams, top management teams, global virtual teams, family businesses, international joint ventures, and strategic alliances.

scholarly journals Sex- and age-specific effects of energy intake and physical activity on sarcopenia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu Jin Cho ◽  
Youn-Hee Lim ◽  
Jae Moon Yun ◽  
Hyung-Jin Yoon ◽  
Minseon Park
Keyword(s):  
Physical Activity ◽  
Energy Intake ◽  
Reference Group ◽  
Multivariate Logistic Regression Analysis ◽  
Young Male ◽  
Young Female ◽  
Mean Value ◽  
Female Group ◽  
Young Females ◽  
Increased Risk

Abstract Sarcopenia is a common health issue that is not limited to only elderly patients. However, many studies have reported factors to prevent sarcopenia only in susceptible groups. This study evaluates the relationship of the total energy intake to basal metabolic rate ratio (EI/BMR) and physical activity (PA) with sarcopenia. A second aim was to analyze the interaction between EI/BMR and PA by sex and age. We analyzed 16,313 subjects aged ≥ 19 years who had dual‒energy X-ray absorptiometry data. Sarcopenia was defined as appendicular lean mass/weight (%) that was 1 standard deviation below the sex-specific mean value for a young reference group. Multivariate logistic regression analysis was used to examine the interaction between EI/BMR and PA. In this study, as EI/BMR increased, the risk of sarcopenia decreased, particularly in the older groups. Both high PA and high EI/BMR were independently related to the reduced risk of sarcopenia and showed additive effects on reducing the risk in young male and older groups. However, high PA was associated with an increased risk of sarcopenia in the young female group with low energy intake. Our findings suggest that an adequate balance between energy intake and PA is related to a low risk of sarcopenia, especially in young females.

New wave of playwriting

Maska ◽  
2020 ◽  
Vol 35 (200) ◽  
pp. 53-67
Author(s):  
Varja Hrvatin
Keyword(s):  
Structural Analysis ◽  
Young Male ◽  
Short Review ◽  
Young Female ◽  
New Wave ◽  
Current Position ◽  
Starting Point ◽  
New Generation ◽  
Open The Doors ◽  
Insight Into

New Wave of Playwriting is a compilation of two editions of the theatre segment Teritorij teatra (The Territory of Theatre) that were broadcast on Radio Študent. In the play of the introductory drama-radio form of the dialogue between the young female playwright and the young male director, it enters the field of exploring the contemporary playwriting of the youngest generation and its current position. For the starting point of the topical-structural analysis of concrete plays, the author takes the call for the Slavko Grum Award for Young Playwright and dedicates her attention to its recipients up to the year 2018. As a counterpoint, she presents various educational, staging or publication initiatives that open the doors for young playwrights. Through a short review of playwrights and their texts, the contribution offers an insight into the new generation of contemporary playwriting; by treating the topics, styles and forms that are popular among playwrights, the article aims to close the gap in the area of reflective analysis.

scholarly journals Changes in Experimental Stroke Outcome across the Life Span

2009 ◽  
Vol 29 (4) ◽  
pp. 792-802 ◽  
Author(s):  
Fudong Liu ◽  
Rongwen Yuan ◽  
Sharon E Benashski ◽  
Louise D McCullough
Keyword(s):  
Life Span ◽  
Cellular Response ◽  
Young Male ◽  
The Elderly ◽  
Young Female ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Elderly Age ◽  
Edema Formation ◽  
Female Mice

Acute ischemic stroke is a leading cause of mortality and disability in the elderly. Age is the most important nonmodifiable risk factor for stroke, yet many preclinical models continue to examine only young male animals. It remains unclear how experimental stroke outcomes change with aging and with biologic sex. If sex differences are present, it is not known whether these reflect an intrinsic differing sensitivity to stroke or are secondary to the loss of estrogen with aging. We subjected both young and aging mice of both sexes to middle cerebral artery occlusion (MCAO). Young female mice had smaller strokes compared with age-matched males, an effect that was reversed by ovariectomy. Stroke damage increased with aging in female mice, whereas male mice had decreased damage after MCAO. Blood–brain barrier (BBB) permeability changes are correlated with infarct size. However, aging mice had significantly less edema formation, an effect that was independent of sex and histologic damage. Differences in the cellular response to stroke occur across the life span in both male and female mice. These differences need to be considered when developing relevant therapies for stroke patients, the majority of whom are elderly.

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