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PubMed2001

The role of public clinics in preventable hospitalizations among vulnerable populations.

OBJECTIVE: To determine if the availability of public ambulatory clinics affects preventable hospitalization (PH) rates of low-income and elderly populations. DATA SOURCES: PH rates were calculated using elderly and low-income discharges from 1995-97 Virginia hospital discharge data. Other data sources include the 1990 Census, the 1998 Area Resource File, the 1996 American Hospital Association Survey, the Virginia Department of Health, the Virginia Primary Care Association, and the Bureau of Primary Health Care. STUDY DESIGN: Multiple linear regression was used to evaluate the relationship between ambulatory clinic availability and PH rates, controlling for population and other provider characteristics in a cross-section of zip code clusters. DATA EXTRACTION METHODS: Clusters with populations of at least 2,000 were assembled from zip codes in each county in the state of Virginia. Overlapping medical market service areas were constructed around the population centroid of each cluster. PRINCIPAL FINDINGS: Populations in medically underserved areas (MUAs) served by a Federally Qualified Health Center had significantly lower PH rates than did other MUA populations. The presence of a free clinic had a marginally significant association with lower PH rates. CONCLUSIONS: The availability of public ambulatory clinics is associated with better access to primary care among low-income and elderly populations.

Adolescent↗
PubMed2002

Gene discovery and microarray analysis of cacao (Theobroma cacao L.) varieties.

The cacao bean harvest from the relatively under developed tropical tree cacao (Theobroma cacao L.) is subject to high losses in potential production due to pests and diseases. To discover and understand the stability of putative natural resistance mechanisms in this commodity crop, essential for chocolate production, we undertook a gene-discovery program and demonstrated its use in gene-expression arrays. Sequencing and assembling bean and leaf cDNA library inserts produced a unique contig set of 1,380 members. High-quality annotation of this gene set using Blast and MetaFam produced annotation for 75% of the contigs and allowed us to identify the types of gene expressed in cacao beans and leaves. Microarrays were constructed using amplified inserts of the uni-gene set and challenged with bean and leaf RNA from five cacao varieties. The microarray performed well across the five randomly chosen cacao genotypes and did not show a bias towards either leaf or bean tissues. This demonstrates that the gene sequences are useful for microarray analysis across cacao genotypes and tissue types. The array results, when compared with real-time PCR results for selected genes, showed a correlation with differential gene-expression patterns. We intend that the resultant DNA sequences and molecular microarray platform will help the cacao community to understand the basis, likely stability and pathotype resistance range of candidate cacao plants.

Cacao↗
PubMed2006

Shedding genomic light on Aristotle's lantern.

Sea urchins have proved fascinating to biologists since the time of Aristotle who compared the appearance of their bony mouth structure to a lantern in The History of Animals. Throughout modern times it has been a model system for research in developmental biology. Now, the genome of the sea urchin Strongylocentrotus purpuratus is the first echinoderm genome to be sequenced. A high quality draft sequence assembly was produced using the Atlas assembler to combine whole genome shotgun sequences with sequences from a collection of BACs selected to form a minimal tiling path along the genome. A formidable challenge was presented by the high degree of heterozygosity between the two haplotypes of the selected male representative of this marine organism. This was overcome by use of the BAC tiling path backbone, in which each BAC represents a single haplotype, as well as by improvements in the Atlas software. Another innovation introduced in this project was the sequencing of pools of tiling path BACs rather than individual BAC sequencing. The Clone-Array Pooled Shotgun Strategy greatly reduced the cost and time devoted to preparing shotgun libraries from BAC clones. The genome sequence was analyzed with several gene prediction methods to produce a comprehensive gene list that was then manually refined and annotated by a volunteer team of sea urchin experts. This latter annotation community edited over 9000 gene models and uncovered many unexpected aspects of the sea urchin genetic content impacting transcriptional regulation, immunology, sensory perception, and an organism's development. Analysis of the basic deuterostome genetic complement supports the sea urchin's role as a model system for deuterostome and, by extension, chordate development.

Animals↗
PubMed2001

International response to the HIV/AIDS epidemic: planning for success.

More assertive political leadership in the global response to AIDS in both poor and rich countries culminated in June 2001 at the UN General Assembly Special Session on AIDS. Delegates made important commitments there, and endorsed a global strategy framework for shifting the dynamics of the epidemic by simultaneously reducing risk, vulnerability and impact. This points the way to achievable progress in the fight against HIV/AIDS. Evidence of success in tackling the spread of AIDS comes from diverse programme areas, including work with sex workers and clients, injecting drug users, and young people. It also comes from diverse countries, including India, the Russian Federation, Senegal, Thailand, the United Republic of Tanzania, and Zambia. Their common feature is the combination of focused approaches with attention to the societywide context within which risk occurs. Similarly, building synergies between prevention and care has underpinned success in Brazil and holds great potential for sub-Saharan Africa, where 90% reductions have been achieved in the prices at which antiretroviral drugs are available. Success also involves overcoming stigma, which undermines community action and blocks access to services. Work against stigma and discrimination has been effectively carried out in both health sector and occupational settings. Accompanying attention to the conditions for success against HIV/AIDS is global consensus on the need for additional resources. The detailed estimate of required AIDS spending in low- and middle-income countries is US$ 9.2 billion annually, compared to the $ 2 billion currently spent. Additional spending should be mobilized by the new global fund to fight AIDS, tuberculosis and malaria, but needs to be joined by additional government and private efforts within countries, including from debt relief. Commitment and capacity to scale up HIV prevention and care have never been stronger. The moment must be seized to prevent a global catastrophe.

Anti-HIV Agents↗
PubMed1996

On the history of modern resuscitation.

The development of modern cardiopulmonary-cerebral resuscitation (CPCR) has given every person the ability to challenge death anywhere. Despite sparks of knowledge and occasional applications of possibly effective lifesaving efforts since antiquity, the possibility to reverse acute terminal states or clinical death by modern, physiologically sound, and effective measures did not come about until around 1900 inside hospitals, and around 1960 outside hospitals. Additional potentially effective cerebral resuscitation, research since around 1970, may be taken to clinical trials before the year 2000. The history of resuscitation medicine around 1900, when many opportunities to assemble existing bits of knowledge into an effective system were missed, should be a warning for those individuals who will lead CPCR beyond the year 2000. History has shown the need for continuing communication and collaboration among investigators of different countries, and between laboratory researchers, clinicians of various disciplines, and prehospital rescuers. The lessons learned from history, for research challenges in the near future, include: a) the development of ultra-advanced life support to be initiated outside the hospital, to bridge cardiopulmonary resuscitation (CPR)-resistant cases to definitive cardiac procedures in the hospital; and b) cerebral resuscitation to complete recovery after 10 to 15 mins of normothermic cardiac arrest without blood flow. Both challenges above will require research projects at multiple levels--from the molecular and cellular levels, to the use of small and large animal models (with organs' and organisms' process and outcome evaluations), to studies of patients and communities. Beyond the year 2000, resuscitation research might become more challenging and cost-effective in the area of multiple trauma, which concerns the young and fit. Research challenges concerning brain trauma, uncontrolled hemorrhagic shock, and "suspended animation" for delayed resuscitation have their own histories, and are not covered here. The author apologizes for not having recognized many important contributors to the history of CPCR because of space constraints or lack of knowledge about such contributions. Input on this subject from readers of this paper is hereby invited.

Cardiopulmonary Resuscitation↗
PubMed2001

A gender difference in the association between APOE genotype and age-related cognitive decline.

OBJECTIVE: To determine whether the APOE epsilon4 allele is associated with age-related intellectual decline in a community-dwelling sample of Danes. METHODS: A sample of 189 subjects who did not have dementia was tested with the Wechsler Adult Intelligence Scale (WAIS) at the ages of 50 and 80 years. Of these subjects, 163 (84 women and 79 men) completed all WAIS subtests at both assessments and 139 completed the digit symbol and block design subtests at the ages of 50, 60, 70, and 80 years. RESULTS: Cognitive decline from the age of 50 to the age of 80 years was substantial and larger for the performance subtests than for the verbal subtests (the declines were 18.40 for the performance IQ and 8.39 for the verbal IQ). APOE genotype was unrelated to the observed WAIS results of the 80-year assessment, but there was a significant interaction between APOE genotype and sex for decline scores in the performance IQ and three performance subtests (digit symbol, block design, and object assembly). In women, 26 epsilon4 carriers showed larger decline than 58 noncarriers, whereas there was no significant relation between APOE genotype and cognitive decline in men. The association in women between APOE genotype and cognitive decline was significant only for decline in the decade from age 70 to age 80 years. The interaction between sex and APOE genotype remained significant when education was included as a covariate. CONCLUSION: The APOE epsilon4 allele is associated with normal age-related decline in cognitive functions in women only. This finding may be supportive of recent evidence suggesting sex differences in APOE-associated risk for AD. Thus, the sex difference in the risk of sporadic AD may partly be explained by a sex-specific impact of the APOE epsilon4 allele on age-related cognitive decline.

Aged↗
PubMed1984

An evaluation of 820 orbital cases.

Eight hundred twenty clinical orbital cases have been reviewed as seen over a 34-year period. These are tabulated as to classification, numbers, and percentages. They include biopsy-proven (450 cases) and other clinical cases. These are patients seen by ophthalmologists practicing in an average community area rather than a large referral center and thus may be more truly representative of what might be encountered in practice. Any series has a certain bias. The advantage of a biopsy-proven series is recognized for the certainty and prognostic aspect. A clinical series represents a wider practical correlation and may include cases not likely to be biopsied, such as hemangioma. It is hoped that the percentage figures of these types of cases will help the clinician in his diagnostic evaluation of patients with orbital lesions. In this series 34% of the orbital lesions were malignant which warrants an aggressive approach for such cases rather than conservative supervision. Because of the very limited number or absence of some types of cases even in a large clinical or biopsy-proven series, I feel it warrants the development of a standard classification of lesions to be used by everyone. Also, assembling the data on infrequent types of lesions from a number of medical centers would give a much larger series and would have a more meaningful prognostic significance. This might be accomplished through one of our national ophthalmologic societies.

Adolescent↗
PubMed1997

Genetic characterization of the rotavirus nonstructural protein, NSP4.

The rotavirus nonstructural protein NSP4 plays a role in viral assembly by acting as an intracellular receptor for single-shelled particles and assisting in the translocation of these particles across the endoplasmic reticulum. Recently, NSP4 has been implicated in rotavirus virulence and is thought to act as an enterotoxin which triggers chloride secretion by a calcium-dependent signal transduction pathway. Limited sequence analysis of NSP4 shows a well-conserved protein. To define the extent of sequence variation in the gene coding for NSP4, we have sequenced this gene from nine human rotavirus strains. These data and the analysis of additional human strains and various animal rotaviruses (bovine, simian, equine, and porcine) by Northern blot hybridization suggested that three NSP4 genotypes were present among rotavirus strains. A correlation between NSP4 genotype and VP6 subgroup was also implied. Two different NSP4 genes (which encoded distinct types of NSP4 proteins) were found among standard human rotaviruses and in strains circulating in the local community and these showed homology to cognate genes in some animal strains.

Amino Acid Sequence↗
PubMed2026

CanVar-UK: A collaborative platform for germline interpretation in cancer susceptibility genes.

Germline variants in cancer susceptibility genes (CSGs) are typically inherited rather than arising de novo. Hence, wide cascade testing of families across geographies is common, meaning consistency in variant classification is particularly critical. Variant interpretation requires collation of variant-level data from diverse sources, as well as assembly of comprehensive clinical data, often necessitating sharing of information between genomic testing centers. Here, we describe CanVar-UK, a freely accessible web platform bespoke designed to support interpretation of germline CSG variants. CanVar-UK contains variant-level data for over 1.1 million single-nucleotide variants (SNVs), comprising all possible coding SNVs in 116 established CSGs. The data sources with which variants are annotated include in silico scores from 11 clinically relevant tools, population allele frequencies from gnomAD v4.1, case counts from multiple cohorts, including National Health Service (NHS) clinical laboratory testing, variant-level readouts from 47 selected functional and splicing datasets across 19 CSGs, genetic epidemiology studies, and live linkage to existing consensus classifications in the ClinVar database. The diagnostic discussion forum is only available to registered diagnostic scientist users. Through this, a variant-tagged email message can be dispatched in real time across the diagnostic forum community of >1,500 users, with all exchanges and classifications captured and stored in the platform. Already widely used by NHS diagnostic clinical scientists in the UK, CanVar-UK has a rapidly growing international diagnostic user base (>800 UK and >600 non-UK registered users). Survey of the NHS diagnostic user community illustrates the wide-ranging utility of CanVar-UK within their clinical workflows for interpretation of germline CSG variants.

Journal Article↗
PubMed2005

Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes.

Autoimmune disorders constitute a diverse group of phenotypes with overlapping features and a tendency toward familial aggregation. It is likely that common underlying genes are involved in these disorders. Until very recently, no specific alleles--aside from a few common human leukocyte antigen class II genes--had been identified that clearly associate with multiple different autoimmune diseases. In this study, we describe a unique collection of 265 multiplex families assembled by the Multiple Autoimmune Disease Genetics Consortium (MADGC). At least two of nine "core" autoimmune diseases are present in each of these families. These core diseases include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), autoimmune thyroid disease (Hashimoto thyroiditis or Graves disease), juvenile RA, inflammatory bowel disease (Crohn disease or ulcerative colitis), psoriasis, and primary Sjogren syndrome. We report that a recently described functional single-nucleotide polymorphism (rs2476601, encoding R620W) in the intracellular tyrosine phosphatase (PTPN22) confers risk of four separate autoimmune phenotypes in these families: T1D, RA, SLE, and Hashimoto thyroiditis. MS did not show association with the PTPN22 risk allele. These findings suggest a common underlying etiologic pathway for some, but not all, autoimmune disorders, and they suggest that MS may have a pathogenesis that is distinct from RA, SLE, and T1D. DNA and clinical data for the MADGC families are available to the scientific community; these data will provide a valuable resource for the dissection of the complex genetic factors that underlie the various autoimmune phenotypes.

Autoimmune Diseases↗
PubMed1997

Better working conditions won by 'nurse wave' action: Japanese nurses' experience of getting a new law by their militant campaign.

Japanese nurses, like their counterparts in many other countries, are suffering from staff shortages and severe working conditions. The Japan Federation of Medical Workers' Unions (Nihon Iroren) launched a campaign in 1989 for nurses called the 'Nurse Wave'. Their demands were many: to increase the numbers of nursing staff, the regulation of night shifts, the implementation of a five-day working week everywhere, a fair appraisal of nurses' work, better vocational training, etc. Nurses in white uniforms assembled at meetings, marched and took part in nation-wide strikes. They collected over 5.4 million petition signatures, which they submitted to Parliament. After three years of campaigning, they won the enactment of a law for securing sufficient numbers of nursing personnel. This struggle, which highlighted the most pressing demands of nurses and was supported by the general public, was a new experience for Japanese nurses. It was a militant movement which demanded that the Government should change its health policy. Against the sluggish image of the Japanese labour movement, strikes and demonstrations organized by nurses dressed in white have made a strong impression on the Japanese people. As health care is a public service on which the life and death of people depend, a strike at a health institution naturally has constraints and must follow specific procedures. In this article, the measures taken by Nihon Iroren to minimize the consequences of strikes on patients and the local community, the impact of the nurses' movement on the society, as well as the lessons drawn from the campaign, are presented.

Humans↗
PubMed2025

Evaluation of sequencing reads at scale using rdeval.

MOTIVATION: Large sequencing datasets are being produced and deposited into public archives at unprecedented rates. The availability of tools that can reliably and efficiently generate and store sequencing read summary statistics has become critical. RESULTS: As part of the effort by the Vertebrate Genomes Project (VGP) to generate high-quality reference genomes at scale, we sought to address the community's need for efficient sequence data evaluation by developing rdeval, a standalone tool to quickly compute and interactively display sequencing read metrics. Rdeval can either run on the fly or store key sequence data metrics in tiny read 'snapshot' files. Statistics can then be efficiently recalled from snapshots for additional processing. Rdeval can convert fa*[.gz] files to and from other popular formats including BAM and CRAM for better compression. Overall, while CRAM achieves the best compression, the gain compared to BAM is marginal, and BAM achieves the best compromise between data compression and access speed. Rdeval also generates a detailed visual report with multiple data analytics that can be exported in various formats. We showcase rdeval's functionalities using long-read data from different sequencing platforms and species, including human. For PacBio long-read sequencing, our analysis shows dramatic improvements in both read length and quality over time, as well as the benefit of increased coverage for genome assembly, though the magnitude varies by taxa. AVAILABILITY AND IMPLEMENTATION: Rdeval is implemented in C++ for data processing and in R for data visualization. Precompiled releases (Linux, MacOS, Windows) and commented source code for rdeval are available under MIT license at https://github.com/vgl-hub/rdeval. Documentation is available on ReadTheDocs (https://rdeval-documentation.readthedocs.io). Rdeval is also available in Bioconda and in Galaxy (https://usegalaxy.org). An automated test workflow ensures the consistency of software updates.

Software↗
PubMed2005

A human-curated annotation of the Candida albicans genome.

Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications.

Journal Article↗
PubMed2006

Agricultural biodiversity, nutrition, and health: making a difference to hunger and nutrition in the developing world.

BACKGROUND: In spite of the strides made globally in reducing hunger, the problems of micronutrient deficiencies and coexisting obesity and related cardiovascular and degenerative diseases constitute a formidable challenge for the future. Attempts to reverse this trend with single-nutrient intervention strategies have met with limited success, resulting in renewed calls for food-based approaches. The deployment of agricultural biodiversity is an approach that entails greater use of local biodiversity to ensure dietary diversity. OBJECTIVE: To outline a new strategy proposed by the International Plant Genetic Resources Institute (IPGRI) that employs agricultural biodiversity as the primary resource for food security and health. METHODS: The authors carried out a meta-analysis to review and assemble existing information on the nutritional and healthful properties of traditional foods based on a diverse set of case studies and food composition and nutritional analysis studies. The methods highlight particular examples of foods where analysis of nutrient and non-nutrient composition reveals important traits to address the growing problems of malnutrition associated with the rise of chronic diseases. Finally, the authors analyze social, economic, and cultural changes that undermine the healthful components of traditional diets. RESULTS: Based on this multidisciplinary and comparative approach, the authors suggest a holistic food-based approach that combines research to assess and document nutritional and healthful properties of traditional foods, investigating options in which nutritionally valuable traditional foods can contribute to better livelihoods, and ways that awareness and promotional campaigns can identify healthful components of traditional diets that fit the needs of urban and market-oriented consumers. CONCLUSIONS: There is an urgent need for agricultural research centers, national agricultural research systems, universities, and community-based organizations to work together under a shared policy framework with the aim of developing a strong evidence base linking biodiversity, nutrition, and health. Although these initiatives are still ongoing, the gains realized in small-scale and local pilot efforts have encouraged IPGRI to work with local partners toward the implementation of scale-up efforts in various regions.

Biodiversity↗
PubMed2026

Ethanol pretreatment drives microbial community adaptation to overcome acidification in high-solid anaerobic digestion of food waste under rapid organic loading shock.

This study investigated how ethanol pretreatment (EP) enhances the resilience of high-solid anaerobic digestion against rapid organic loading shocks. Semi-continuous reactors fed with either untreated or EP-treated food waste were compared, and the underlying mechanisms were elucidated by integrating thermodynamic calculations with metagenomic analyses. At an organic loading rate of 6.0 g VS/(Lˑd), the control group (untreated) collapsed due to the accumulation of propionate and other longer-chain volatile fatty acids (VFAs), resulting in a methane yield decrease exceeding 70%. In contrast, the EP group maintained stability, exhibiting a methane yield decrease of less than 5%, with VFAs dominated by readily degradable acetate. Thermodynamic analysis confirmed that EP significantly lowered the energy barriers for VFA degradation. Metagenomic analysis revealed that both propionate/butyrate activation pathways (with lower energy cost or independence from acetyl-CoA) and syntrophic acetate oxidation were activated in the EP group, thereby avoiding the VFA metabolic stress observed in the control group. Furthermore, higher abundances of conductive type IV pili genes, Complex II, and archaeal V/A-type ATPase were detected in the EP group, suggesting the establishment of direct interspecies electron transfer and enhanced electron flux and energy capture efficiency. Moreover, under high loading conditions, only a few high-abundance metagenome-assembled genomes (MAGs) were detected in the control group, while multiple MAGs carrying identical VFA-degrading enzyme systems were identified in the EP group. The functionally redundant microbiota, unobstructed VFA metabolic pathways, and efficient electron transfer and energy supply collectively sustained the stability of the EP group under loading shocks.

Anaerobic digestion↗
PubMed2005

Process evaluation of the New South Wales Walk Safely to School Day.

ISSUES ADDRESSED: Concerns about the contribution of lower physical activity by children on levels of childhood obesity have driven the search for interventions that encourage lifestyle physical activity by school-aged children. METHOD: This paper describes the evaluation of the New South Wales (NSW) Walk Safely To School Day (WSTSD), an event repeated annually on the first Friday in April from 2001 to 2004. Paid media advertising before the event promoted WSTSD. All primary schools in NSW were invited to participate. The evaluation included monitoring of schools registering to participate over four years, and in 2002 evaluation feedback from schools as well as a population-based telephone survey of randomly selected parents of primary school-aged children. RESULTS: By 2004, 53% of all primary schools in NSW had participated at least once in WSTSD and 15% had participated for at least three years. Participating schools linked WSTSD to road safety curricula, and 59% of schools also talked about WSTSD at school assemblies, but few (7%) organised walking-related activities. Parents reported that one-quarter (24%) of NSW primary school-aged students participated in WSTSD activities, including an additional 31% more children walking to school on WSTSD than would normally walk on a Friday. CONCLUSION: Walk Safely To School Day resulted in a moderate short-term change in walking behaviour. High levels of in-principle support from parents indicate that greater participation in walking to school is possible, but will require stronger interventions to overcome the barriers identified by parents and to maintain changes.

Awareness↗
PubMed2004

Oocyte maturation and cell cycle control: a farewell symposium for Pr Marcel Dorée.

Oocyte maturation and early development have been intensively studied for well over 100 years. The earliest theory proposed that after fertilisation and during cell division determinants were unequally distributed to control cell fate; experimental proof came from using frog eggs (Roux, 1888). After understanding the contribution of the nucleus and the chromosomes into cell cycle progression using sea urchin eggs (Boveri, 1902), it was the discovery of the cytoplasm contribution to the G2/M transition that led the cell cycle community in search of the "mitosis-inducing factor", MPF. Yoshio Masui was the first to experimentally demonstrate that few nanoliters of cytoplasm taken from a metaphase-arrested oocyte and microinjected in a G2-arrested oocyte was able to trigger the G2 to metaphase transition (Masui and Markert, 1971). Although the way to identify the mitotic factor seemed obvious, it proved very hard and was not purified until 1988 (Lohka et al, 1988), then work from a variety of organisms including Xenopus, starfish, clams, sea urchins and yeast converged on the identification of MPF as a complex of cdc2 and cyclin B (Dunphy et al, 1988; Gautier et al., 1988; Draetta et al., 1889; Meijer et al., 1989; Labbé et al., 1989; Gautier et al., 1990). Since then, the oocyte and egg extracts developed by Lohka and Masui have often been used to study cell cycle events such as nuclear envelop formation, chromatin condensation, DNA replication, repair, and recombination, Golgi formation, microtubule dynamics, spindle assembly, chromosome segregation as well as cell cycle controls.

Animals↗