Life during Dormancy: Genetic Regulation in Fission Yeast Spores and in Killifish Diapause

Dormant stages allow organisms to survive in life-threatening environments for extended periods of time. Dormancy is characterised by a reversible arrest of cell replication and increased stress resistance. In addition, dormancy involves reprogramming of gene expression and energy metabolism from a mode of proliferation and development to a mode of suspended growth, possibly including suspended ageing. Here I study the spores of fission yeast and diapause embryos of turquoise killifish to reveal similarities in transcriptome and proteome changes during dormancy. Moreover, I uncover some conservation in the genetic regulation of dormancy and halted ageing across different organisms and dormant stages, including yeast quiescence and worm dauer stages. In particular, I find ribosomal proteins and autophagy play critical roles in supporting dormancy in yeast and killifish. Supporting this result, functional analysis using Barcode sequencing of the genome-wide deletion library for fission yeast identifies ribosomal proteins and autophagy as important factors for survival during dormancy. Furthermore, while traditionally it has been assumed that spores in yeast and diapause in killifish equate to suspension biological activity, I find that both dormant states can respond to environmental or physiological triggers by altering their gene-expression programmes. Specifically, this response includes proteomic and transcriptomic changes to heat stress as well as changes with the chronological passing of time following their formation. While some of these genetic changes mimic non-dormant yeast stress responses, they differ from expression signatures observed during ageing. This finding is consistent with the idea that dormant yeast and killifish cells are not ageing in the same manner as non- dormant cells, or that ageing is even suspended during dormancy. Finally, as dormant stages are a state of suspended activity, events occurring during the dormant stage are not thought to affect the organism in post-dormant cells. Intriguingly, I find that the stress experienced during dormancy and the duration the organism stays in dormancy is ‘remembered’ and can affect post-dormancy recovery in both yeast and killifish. This phenomenon is evidenced by changes in gene expression profiles. I also observe subtle differences in stress resistance and chronological lifespan in germinates from stressed or old spores. This is exhibited by a type of hormesis where sub-lethal stress during dormancy might confer a slight lifespan extension in the post-dormant state. These new insights transform our understanding of “dormant states” and the implication of dormancy to post-dormancy stress survival and ageing

Toward new dominations: Flawed devotions to human rights discourse and its contingent hope

Human rights movement dominates over how people articulate their interests to be heard. It controls massive resources in the name of those interests. This dissertation articulates a path for new emancipation projects to hinder the domination of the human rights movement. Devotion to the movement maintains the illusion of objectifying people’s interests outside politics. Though, the movement fails to deliver on that objectification when activists choose between competing interests, deferring their failures to the future. That temporal space holds the movement’s universal claim. The instability of the movement lies in the gap between what it promises and what it delivers, creating its emancipatory and imperial sides. I argue that the present gets filled up with development towards economic growth, which justifies the universal claims of the movement while the movement justifies the absence of development. The movement acquires the role of representing the universal function with the aid of development. Power holds that representation, which becomes contingent. The contingency of the representation of the universal function is hopeful for different emancipation movements to compete along the human rights discourse. I retain the universal as an empty ground to disprove the fullness of the universal function. Then, I move to suggest that the Other, with the plurality inside that category, can either struggle for the representation for the universal function or for utilizing the emancipatory side of the rights discourse. I choose the former. I urge new liberation projects to fight for the representation of the universal function, without essentializing the subaltern voices, since all Other(s) can struggle their way(s) towards new forms of dominations. Essentializing the subaltern voices within the plurality gains them recognition within the hegemonic. But, I fight for the liberation in struggling rather than recognition; for the Other(s)’ laments to dominate over the rights’ laments

Investigation of the Nuclear Structure of Some Ni and Zn Isotopes with Skyrme-Hartree-Fock Interaction

تم التقصي عن عوامل التشكل C2 الغير مرن  وتوزيع كثافة الشحنة (CDD) لـ 58,60,62Ni  و 64,66,68Zn  من خلال استخدام طريقة Skyrme-Hartree-Fock مع معلمات (Sk35-Skzs *). تم حساب عوامل التشكل C2 غير المرن باستخدام شكل نماذج Tassie و Bohr-Mottelson مع الشحنات الفعالة المناسبة للبروتون والنيوترون لحساب مساهمة تأثيرات أستقطاب القلب. تمت مقارنة القيم النظرية المتوقعة مع البيانات المقاسة المتاحة لعوامل الشكل C2 و CDD وأظهرت توافقًا جيدًا جدًا.The inelastic C2 form factors and the charge density distribution (CDD) for 58,60,62Ni and 64,66,68Zn nuclei has been investigated by employing the Skyrme-Hartree-Fock method with (Sk35-Skzs*) parametrization. The inelastic C2 form factor is calculated by using the shape of Tassie and Bohr-Mottelson models with appropriate proton and neutron effective charges to account for the core-polarization effects contribution. The comparison of the predicted theoretical values was conducted with the available measured data for C2 and CDD form factors and showed very good agreement

Antimicrobial Effect of Eco- Friendly Silver Nanoparticles Synthesis by Iraqi Date Palm (Phoenix dactylifera) on Gram-Negative Biofilm-Forming Bacteria

يعد تصنيع دقائق الفضة النانوية بواسطة التمر بالطريقة الخضراء او النباتية واستخدامه كمضاد بكتيري. في الوقت الحاضر حصلت هذه الطريقة على اهتمام الباحثين النها امينة وغير سامة وقليلة التكلفة وصديقة للبيئة. تشتمل البكتريا المكونة للغشاء الحيوي والموجودة في الحليب المحلي المتوفر باالسواق على خطورة عالية على صحة المجتمع بسبب ان اغلب البكتريا المكونة للغشاء الحيوي تكون مقاومة للمضادات الحياتية. الهدف من الدراسة هو القضاء على البكتريا المكونة للغشاء الحيوي والموجودة بالحليب المحلي باستخدام عالجا بديال بتحضير دقائق الفضة النانوية من التمر. حيث كشفت قابلية البكتريا المعزولة من الحليب المحلي على تكوين الغشاء الحيوي باستخدام طريقة صبغة الكونغو الحمراء. حضرت دقائق الفضة النانوية باستخدام خالصة التمر. حيث تم فحص دقائق الفضة المصنوعة بواسطة جهاز االشعة فوق البنفسجية ومجهر القوة الذرية. تم تقييم فاعلية دقائق الفضة المصنعة المضادة للبكتريا بواسطة طريق االنتشار الحفر باألكار. اظهرت النتائج ان البكتريا المعزولة من الحليب والمنتجة للغشاء الحيوي هي االشرشيا القولونيةcoli. E بعدد 3 وال pneumoniae Klebsiellaبعدد 5 عزالت ضمن العزالت السالبة لصبغة غرام. حجم النانو المحضر كان 35 نانوميتر حيث تم الكشف عن تكونه بواسطة التغيير اللوني للمستخلص النباتي من اللون االصفر الى البني وقمة امتصاص عند 410 نانوميتر. كذلك اظهرت النتائج عن الفاعلية العالية لدقائق الفضة في القضاء على البكتريا السالبة لصبغة غرام و المنتجة للغشاء الحيوي. نستنتج من هذه الدراسة ان دقائق الفضة المصنعة من مستخلص التمر ذو كفاءة عالية في القضاء على البكتريا السالبة لصبغة غرام والمنتجة للغشاء الحيوي.Date palm silver nanoparticles are a green synthesis method used as antibacterial agents. Today, there is a considerable interest in it because it is safe, nontoxic, low costly and ecofriendly. Biofilm bacteria existing in marketed local milk is at highly risk on population health and may be life-threatening as most biofilm-forming bacteria are multidrug resistance. The goal of current study is to eradicate biofilm-forming bacteria by alternative treatment green synthesis silver nanoparticles. The biofilm formation by bacterial isolates was detected by Congo red method. The silver nanoparticles were prepared from date palm(khestawy) fruit extract. The formed nanoparticles were characterized with UV-Vis and AFM. The antibacterial activity of synthetic silver nanoparticles was evaluated by agar well diffusion method. Gram-negative bacteria isolates were E. coli in 3 isolates and Klebsiella pneumoniae in 5 isolates and all are biofilm producer. The size of synthetic green silver nanoparticles is 18 nm and the generation of silver nanoparticles was confirmed by change of date extract color from yellow to brown with an absorption maximum at 410 nm. Highly antibacterial activity of silver nanoparticles was recorded in comparison to plant extract and silver nitrate against gram-negative biofilm-forming bacteria. From this study, the antibacterial activity of date palm silver nanoparticles was more efficient to eradicate gram negative biofilm[1]forming bacteria isolated from marketed local mil

Morphological alterations in the jejunal mucosa of aged rats and the possible protective role of green tea

Introduction. Gastrointestinal disorders become more prevalent with ageing. This study is aimed to describe morphological changes that occur in the jejunal mucosa of male albino rats as a result of ageing and the protec­tive effect of green tea (GT) extract. Material and methods. The experiment was performed on sixty rats: thirty young-adult (6-month old, body mass 200–220 g) and thirty old (24-month-old, body mass 220–260 g) animals. Each group was further divided into two subgroups (n = 15 each): control rats and GT-treated rats that received 1.5 mL (300 mg/kg/day) of GT extract for 14 weeks by oral gavage. Sections of the jejunum were stained with hematoxylin and eosin, periodic acid Schiff, toluidine blue and Mallory trichrome methods. The presence of proliferating cell nuclear antigen (PCNA)- and CD68-positive cells was evaluated by immunohistochemical staining. Ultrathin sections were prepared and examined by a transmission electron microscope (TEM). Results. Jejunal sections of the old control rats showed distortion of submucosa and attenuated muscularis externa with decreased height of intestinal villi. The villi also showed partial loss of acidophilic brush border with wide spaces between enterocytes. Swollen, short, blunt or broad villi with abundant mononuclear cell infiltration of lamina propria and congested blood vessels were evident both by light and electron microscopy. The number of PCNA- and CD68-positive cells in jejunal mucosa of old rats was higher than in young rats. The activity of glutathione peroxidase (GPX) and total antioxidant capacity (TAC) in the mucosa of old control rats were lower, whereas malondialdehyde (MDA) levels were higher in the jejunal homogenates of old rats as compared to young control rats. Administration of GT extract protected the jejunal mucosa from age-related changes by restoring its histological structure. The treatment of old rats with GT extract significantly decreased MDA levels in the jejunum and increased TAC and GPX activity. Conclusions. The age-related changes of the morphology of rat jejunum could be ameliorated by prolonged supplementation of the green tea extract

Broad functional profiling of fission yeast proteins using phenomics and machine learning

Many proteins remain poorly characterized even in well-studied organisms, presenting a bottleneck for research. We applied phenomics and machine-learning approaches with Schizosaccharomyces pombe for broad cues on protein functions. We assayed colony-growth phenotypes to measure the fitness of deletion mutants for 3509 non-essential genes in 131 conditions with different nutrients, drugs, and stresses. These analyses exposed phenotypes for 3492 mutants, including 124 mutants of ‘priority unstudied’ proteins conserved in humans, providing varied functional clues. For example, over 900 proteins were newly implicated in the resistance to oxidative stress. Phenotype-correlation networks suggested roles for poorly characterized proteins through ‘guilt by association’ with known proteins. For complementary functional insights, we predicted Gene Ontology (GO) terms using machine learning methods exploiting protein-network and protein-homology data (NET-FF). We obtained 56,594 high-scoring GO predictions, of which 22,060 also featured high information content. Our phenotype-correlation data and NET-FF predictions showed a strong concordance with existing PomBase GO annotations and protein networks, with integrated analyses revealing 1675 novel GO predictions for 783 genes, including 47 predictions for 23 priority unstudied proteins. Experimental validation identified new proteins involved in cellular aging, showing that these predictions and phenomics data provide a rich resource to uncover new protein functions

Acaricidal activity of tea tree and lemon oil nanoemulsions against Rhipicephalus annulatus

Tick infestation is a serious problem in many countries since it has an impact on the health of animals used for food production and pets, and frequently affects humans. Therefore, the present study aimed to investigate the acaricidal effects of nanoemulsions of essential oils o

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe