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PubMed2025

KIF18A promotes chromosome congression in cooperation with CENP-E downstream of CENP-C.

Chromosome congression is a key process that acts to align chromosomes at the spindle equator via kinetochore-microtubule interactions, with defects in chromosome alignment leading to chromosomal instability. However, defining the mechanisms that underlie chromosome congression is limited due to the multiple factors that act in parallel to regulate chromosome movement. Here, we conducted a genome-wide Cas9-based functional genetics screen using a hypomorphic CENP-C mutant that affects its kinetochore interactions. Our analysis identified KIF18A, whose knockout resulted in synthetic lethality with the CENP-C mutant. Further analysis revealed that the synthetic defect was due to a reduction in CENP-E function in the CENP-C mutant. Our work suggests that KIF18A promotes chromosome alignment in cooperation with CENP-E downstream of CENP-C during early prometaphase. Thus, our analysis enables us to dissect parallel molecular mechanisms for chromosome congression and identify sensitivities and biomarkers that might guide anti-KIF18A chemotherapeutics.

Kinesins↗

PubMed1993

Colorectal cancer in patients under 30 years of age. Contributors to the Southwestern Surgical Congress Unusual Case Registry.

The Southwestern Surgical Congress (SWSC) recently initiated a registry of unusual cases. The registry was created to collect information on patients with uncommon conditions treated by members of the Congress. The registry is intended to be a source of clinical information for the members, as well as a tool for the conduct of retrospective and prospective clinical and epidemiologic studies. As the first project, we collected data on patients with colorectal cancer who were 30 years of age or less at the time of diagnosis. Letters were sent to all members of the SWSC soliciting information about such patients. Data collection sheets were subsequently mailed to those who responded to the letter. The data sheets asked for demographic data, as well as pertinent anamnestic, clinical, and staging information. Operative reports, pathology reports, and paraffin-embedded tissue blocks were also requested. Twenty-four members contributed a total of 55 patients to the registry. There were 23 males (age range: 14 to 30 years) and 32 females (age range: 16 to 30 years). In 37 patients, factors assumed to predispose to colorectal cancer were identified. The most common predisposing factor was smoking. There were 12 right colon tumors, 24 left colon tumors, and 11 rectal tumors. According to the TNM classification, 6 patients had stage I disease, 15 patients had stage II disease, 17 patients had stage III disease, and 17 patients had stage IV disease. Tissue blocks from tumor and adjacent bowel will be examined to address the issue of a possible genetic predisposition for cancer at the molecular level, in these young patients. We will also assess the independent influence of age on prognosis by comparing the actuarial survival and recurrence rates in patients from the registry with data from older patients who are matched for the presence of other known prognostic factors. The Unusual Case Registry will provide the members of the Congress with a valuable database of clinical information. Furthermore, this method of compilation will facilitate the collection of relatively large patient samples over a short period of time. This will greatly facilitate the conduct of original and relevant collaborative prospective studies of uncommon diseases within the framework of the SWSC.

Adolescent↗

PubMed1993

Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push-pull mechanism.

Most models of mitotic congression and segregation assume that only poleward pulling forces occur at kinetochores. However, there are reports for several different cell types that both mono-oriented and bi-oriented chromosomes oscillate toward and away from the pole throughout mitosis. We used new methods of high resolution video microscopy and computer-assisted tracking techniques to measure the positions over time of individual kinetochores with respect to their poles during mitosis in living newt lung cells. The results show that kinetochores oscillate throughout mitosis when they are tethered to spindle poles by attachment to the plus-ends of kinetochore microtubules (kMTs). Oscillations were not sinusoidal. Instead, kinetochores abruptly (as quick as 6 s or less) switched between persistent (approximately 1.5 min average duration) phases of poleward (P) and away from the pole (AP) movement. This kinetochore "directional instability" was a property of motility at the plus-ends of kMTs since fluorescent marks on the lattice of kMTs have previously been observed to exhibit only relatively slow P movement. Each P and AP phase consisted of one or a few constant velocity domains (approximately 1.7 microns/min average velocity). Velocities of P and AP phases were similar from prometaphase through mid-anaphase. Kinetochores occasionally switched to an indeterminant (N) phase of no or confused motion, which was usually brief compared to the durations of P and AP phases. Net chromosome displacements that occurred during congression to the equator or poleward movement during anaphase were primarily generated by differences in the durations and not the velocities of P and AP movements. Careful analysis of centromere deformation showed that kinetochore P movement produced pulling forces while kinetochore AP movement produced pushing forces. These data show that kinetochore directional instability is fundamental to the processes of chromosome congression and segregation. We argue that tension at the kinetochore attachment site is a key factor which controls the switching between P and AP phases of kinetochore motion.

Animals↗

PubMed1997

Kinetochore fiber maturation in PtK1 cells and its implications for the mechanisms of chromosome congression and anaphase onset.

Kinetochore microtubules (kMts) are a subset of spindle microtubules that bind directly to the kinetochore to form the kinetochore fiber (K-fiber). The K-fiber in turn interacts with the kinetochore to produce chromosome motion toward the attached spindle pole. We have examined K-fiber maturation in PtK1 cells using same-cell video light microscopy/serial section EM. During congression, the kinetochore moving away from its spindle pole (i.e., the trailing kinetochore) and its leading, poleward moving sister both have variable numbers of kMts, but the trailing kinetochore always has at least twice as many kMts as the leading kinetochore. A comparison of Mt numbers on sister kinetochores of congressing chromosomes with their direction of motion, as well as distance from their associated spindle poles, reveals that the direction of motion is not determined by kMt number or total kMt length. The same result was observed for oscillating metaphase chromosomes. These data demonstrate that the tendency of a kinetochore to move poleward is not positively correlated with the kMt number. At late prometaphase, the average number of Mts on fully congressed kinetochores is 19.7 +/- 6.7 (n = 94), at late metaphase 24.3 +/- 4.9 (n = 62), and at early anaphase 27.8 +/- 6.3 (n = 65). Differences between these distributions are statistically significant. The increased kMt number during early anaphase, relative to late metaphase, reflects the increased kMt stability at anaphase onset. Treatment of late metaphase cells with 1 microM taxol inhibits anaphase onset, but produces the same kMt distribution as in early anaphase: 28.7 +/- 7. 4 (n = 54). Thus, a full complement of kMts is not sufficient to induce anaphase onset. We also measured the time course for kMt acquisition and determined an initial rate of 1.9 kMts/min. This rate accelerates up to 10-fold during the course of K-fiber maturation, suggesting an increased concentration of Mt plus ends in the vicinity of the kinetochore at late metaphase and/or cooperativity for kMt acquisition.

Anaphase↗

PubMed2001

The chromokinesin Kid is necessary for chromosome arm orientation and oscillation, but not congression, on mitotic spindles.

Chromokinesins have been postulated to provide the polar ejection force needed for chromosome congression during mitosis. We have evaluated that possibility by monitoring chromosome movement in vertebrate-cultured cells using time-lapse differential interference contrast microscopy after microinjection with antibodies specific for the chromokinesin Kid. 17.5% of cells injected with Kid-specific antibodies have one or more chromosomes that remain closely opposed to a spindle pole and fail to enter anaphase. In contrast, 82.5% of injected cells align chromosomes in metaphase, progress to anaphase, and display chromosome velocities not significantly different from control cells. However, injected cells lack chromosome oscillations, and chromosome orientation is atypical because chromosome arms extend toward spindle poles during both congression and metaphase. Furthermore, chromosomes cluster into a mass and fail to oscillate when Kid is perturbed in cells containing monopolar spindles. These data indicate that Kid generates the polar ejection force that pushes chromosome arms away from spindle poles in vertebrate-cultured cells. This force increases the efficiency with which chromosomes make bipolar spindle attachments and regulates kinetochore activities necessary for chromosome oscillation, but is not essential for chromosome congression.

Antibodies, Monoclonal↗

PubMed2000

Schizophrenia research: a progress report, summarizing proceedings of the 1999 International Congress on Schizophrenia Research.

The Seventh International Congress on Schizophrenia Research was held in Santa Fe, New Mexico, in April 1999. This was the largest Congress meeting to date, with almost 1,000 presentations that covered all aspects of schizophrenia research. This article provides an account of the Congress proceedings. Several research areas received extensive coverage, including early detection of illness through the use of cognitive and behavioral precursors of schizophrenia and the etiology and treatment of childhood-onset and first episode schizophrenia. The etiopathophysiological hypothesis of schizophrenia as a disorder of neural dysconnectivity was promoted across cognitive, neurochemical, neuroimaging, and postmortem domains. The importance of cognition as a major outcome measure and the impact of new antipsychotics on the treatment and conceptualization of schizophrenia were also major topics. Overall, the conference was noteworthy for the convergence of findings across research domains.

Adult↗

PubMed2004

'Alukura ... for my daughters and their daughters and their daughters'. A review of Congress Alukura.

OBJECTIVE: To describe the process, findings and limitations of a review of Congress Alukura commissioned in 1998. METHODS: Analysis of documents and reports, service use and perinatal data from Alukura and the Northern Territory Midwives Collection; interviews with staff of Congress Alukura, of Central Australian Aboriginal Congress, of Aboriginal community organisations in Alice Springs and remote communities, of health care providers and other key informants in Alice Springs; community consultations through women's meetings or group discussions in local and remote communities. Interviews were coded for thematic and content analysis. RESULTS: Client visits increased by 42% from 1995/96 (2130) to 1997/98. The proportion of women having a first trimester antenatal visit increased from 23% (1986-88) to 38% (1993-95). Mean birthweight of Aboriginal infants in the Alice Springs urban area was 3168 g in 1986-90, 3271 g in 1991-95, and 3268 g in 1996-99. Other primary and maternity care providers perceived the quality of care to be high and saw Alukura playing a key role through transport, liaison, screening and follow-up. Alukura was much less successful in its role as a place for birth. Expectations of additional outreach by local and remote communities were high. DISCUSSION: The review's limitations included: a lack of direct input from young women, the main users of Alukura; a timeframe that precluded the detailed discussion necessary for seeking access to medical records, and the need for interpreters in community settings. Current and former staff who participated in the review often had other important community roles. Developments since the review are discussed briefly.

Australia↗

PubMed2005

A mitotic septin scaffold required for Mammalian chromosome congression and segregation.

Coordination of cytokinesis with chromosome congression and segregation is critical for proper cell division, but the mechanism is unknown. Here, septins, a conserved family of polymerizing guanosine triphosphate-binding proteins, localized to the metaphase plate during mitosis. Septin depletion resulted in chromosome loss from the metaphase plate, lack of chromosome segregation and spindle elongation, and incomplete cytokinesis upon delayed mitotic exit. These defects correlated with loss of the mitotic motor and the checkpoint regulator centromere-associated protein E (CENP-E) from the kinetochores of congressing chromosomes. Mammalian septins may thus form a mitotic scaffold for CENP-E and other effectors to coordinate cytokinesis with chromosome congression and segregation.

Animals↗

PubMed2001

European Society of Intensive Care Medicine 14th annual congress, 30 September-3 October 2001, Geneva, Switzerland.

The European Society of Intensive Care Medicine Annual Congress offers the opportunity for basic scientists and clinicians to share recent findings. Apart from the large number of free communications, several sessions of the congress were dedicated to state-of-the-art tutorials given by established speakers. The areas of interest of the attendees were widely distributed as usual, a reflection of the large array of so-called 'critical illnesses'. The results of clinical trials and experimental findings using recently developed drugs were presented, essentially in the fields of inflammation, sepsis, and acute lung injury. The benefits of several new compounds observed experimentally need to be confirmed clinically. The European Society of Intensive Care Medicine Congress is well established as a unique opportunity to implement and to promote a collaboration between European basic scientists and clinicians.

Anti-Bacterial Agents↗

PubMed2001

11th International Congress of Endocrinology.

The Olympics of endocrinology, the 11th International Congress of Endocrinolgy was held rather appropriately in Sydney, four weeks after the summer games of the XXWIIth Modern Olympiad. Both occasions were a great success and whilst it may be tempting to extend the analogy to the pool or the track or heaven forbid, digress into 'drugs in sport', this review will focus on endocrinology. There were over 3000 participants with ten plenary lectures, 20 meet-the-expert sessions, 41 symposia, 128 oral free communications and 1500 posters. Sydney post-Olympics provided a vibrant, exciting and picturesque setting with outstanding convention facilities. The Congress Party was held at Campbells Cove in the lee of the Harbour Bridge looking toward the Opera House which provided an opportunity for delegates to view the two architectural icons that had become so familiar in the preceding months. Credit must be given both to the Local Organising Committee of Sydney endocrinologists who made it all happen and to the International Program Organising Committee who crafted a pageant of first rate endocrinology. It is self-evident that this report can only hope to give the reader a flavour of a Congress such as this with the choice of topics being largely idiosyncratic. With five concurrent symposia and two concurrent orals each morning and afternoon of the four days, any omissions reflect not on the topic or its importance but on this reviewer's inability to be in more than one place at once!

Animals↗

PubMed1997

The 20th International Congress of Chemotherapy.

Over 4,000 participants from all over the world attended the 20th International Congress of Chemotherapy (ICC) between 29th June-3rd July, 1997, in Sydney. Anti-infective and cancer chemotherapy were discussed in a wide context, with presentations being made on new products, compounds in development and current clinical approaches. Inevitably in a congress of this size, there were many sessions running concurrently (usually nine), with several simultaneous poster sessions as well. A common theme currently at many chemotherapy congresses is the growth of resistance to existing agents, and the ICC was no exception. Resistance to Gram-positive cocci is a particular problem, and many sessions were devoted to this subject. This report attempts to highlight just some of the aspects of antibacterial chemotherapy presented at the meeting. New fluoroquinolones formed a major topic that attracted a number of poster sessions and symposia, continuing a trend seen in recent years. The streptogramins offer an alternative approach to combating Gram-positive infections, and a symposium was devoted to these compounds.

Journal Article↗

PubMed1972

Fixed-interval work habits of Congress.

The rate at which Congress passes bills during its legislative session exhibits a fixed-interval pattern: the rate of passage is extremely low three to four months after commencement followed by a positively accelerated growth rate that continues until the time of adjournment. This scalloped configuration appears uniformly in each of the eight Congresses sampled, from 1947 to 1968, and in both sessions of each Congress.

Journal Article↗

PubMed1997

National health care reform and the 103rd Congress: the activities and influence of public health advocates.

OBJECTIVES: This study examined the activities and influence of public health interest groups and coalitions on the national health care reform debates in the 103rd Congress. METHODS: Congressional staff and representatives of public health interest groups, coalitions, and government health agencies were interviewed. Content analysis of eight leading national health care reform bills was performed. RESULTS: The public health community coalesced around public health in health care reform; nearly all the major interest groups and government health agencies joined two or more public health or prevention coalitions, and half joined three or more. The most effective influence on health care reform legislation was early, sustained personal contact with Congress members and their staffs, accompanied by succinct written materials summarizing key points. Media campaigns and grassroots mobilization were less effective. Seven of the eight leading health care reform bills included one or more of the priorities supported by public health advocates. CONCLUSIONS: The public health community played an important role in increasing awareness and support for public health programs in the health care reform bills of the 103rd Congress.

Health Care Reform↗

PubMed1981

Ningxia People's Congress adopts marriage law.

A supplement to the national marriage law was adopted by the 3rd session of the 4th People's Congress of the Ningxia Hui Autonomous Region which ended here today. The supplement includes a number of areas. With regard to marriage age it says no marriage shall be contracted before the man has reached 20 years of age and the woman 18. Both these figures are 2 years earlier than the national age specified by the national law. Legal marriage registration must not be replaced by religious ceremonies. With regard to Moslems, those who want religious wedding ceremonies can do so only after obtaining their marriage certificates. Freedom of marriage of widows is protected against any interference under any pretext. Marriage between Hui people and other nationalities, of their own free will, must not be interfered with. The nationality of any children shall be decided by the parents and children may reexamine the decision themselves when they grow up. The supplement has been adopted in accordance with the national marriage law's article 36 which says "The people's congresses and their standing committees in national autonomous areas may enact certain modifications or supplementary articles in keeping with the principles of this law and in conformity with the actual conditions prevailing among the minority nationalities of the locality in regard to marriage and family relations." The congress, held from June 9-June 14, reviewed the implementation of the Communist Party's policies on nationalities and development of economy, culture, education and public health.

Asia↗

PubMed2004

Diagnosis and treatment of MS in Latin America. MS Forum Interactive Symposium at the LACTRIMS Congress, 27 August 2004, Iguazu Falls, Brazil.

The LACTRIMS congress at Foz do Iguacu attracted approximately 500 delegates, representing an important medium for increasing awareness of MS within the neurology community in Latin America. It also provided a forum for neurologists in Latin America, who are already diagnosing and treating patients with MS, to discuss ideas and exchange experiences. This year's congress discussed comprehensive management of patients with MS in Latin America, and how best to achieve this within the context of the local healthcare system. An MS Forum Interactive Symposium formed part of the congress programme and gave attendees the opportunity to learn more about the MS Forum and its activities, as well as managing MS.

Brain↗

PubMed1991

Threatening and otherwise inappropriate letters to members of the United States Congress.

The authors examine the characteristics of threatening and otherwise inappropriate communications sent to members of the U.S. Congress by a sample of 86 subjects, 20 of whom threatened assassination. We quote excerpts from these letters and provide quantitative data on such variables as the volume, duration, form, and appearance of such communications; the enclosures; the subjects' perceived relationships to the recipients; the thematic content of the communications; and the messages and threats communicated. Comparisons between 43 subjects who pursued encounters with members of Congress and 43 who did not revealed 17 factors associated with such pursuit. In this population, threateners were significantly less likely to pursue an encounter than inappropriate letter writers who did not threaten, regardless of the type of threat or the harm threatened. Inappropriate letters to members of Congress are compared with those directed to Hollywood celebrities. Mentally disordered persons writing to public figures often mention and sometimes threaten public figures other than those to whom the letters are addressed, which raises important issues regarding notification of endangered third parties and the sharing of information among protective agencies.

Correspondence as Topic↗

PubMed1978

[Legal and organizational bases of health care in the textile industry of the Congress Kingdom of Poland in the 19th and beginning of 20th cent. (forms of insurance, work safety and sanitary regulations)].

The origins of state interventionism in the field of health care in the textile industry of the Congress Kingdom of Poland go back to the first half of the XIX-th century. It could not, however, be developed earlier than in the last quarter of this century, at which time it resulted from the class struggle of textile workers, mainly in Lódź and Zyraŕdów. Legal and organizational patterns of health care were of foreign origin, but soon they were modified and adapted to the local conditions of the Congress Kingdom of Poland. It has to be underlined that it was the textile industry that stimulated legal and organizational changes in the field of industrial health care, not only in the Congress Kingdom of Poland but also in the whole contemporary Europe.

Accident Prevention↗

PubMed1966

Outlook for restrictive animal legislation in the 89th Congress.

Past records indicate that legislation, be it extreme or moderate in design, will be the goal of the proponents of restrictive animal legislation in the 89th Congress. Bills similar to those introduced in past sessions almost surely will appear again. If the President succeeds in soliciting congressional support for his goals of the Great Society, Congress may have little time for other legislative matters. The medical and scientific forces that oppose the use of federal legislation as a means of upgrading the standards of animal care and improving the validity of the results of biological research can be expected to continue their support of voluntary control through education and research. Continued support of the effective "task forces" and public relations programs that developed during the 88th Congress must come from all segments of the organized health professions.

Animals↗