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At least 253 records · Page 14Linked to original sources
PubMed2000

Neuronal migration defects of the cerebral cortex: a destination debacle.

Disruptions in neuronal migration have been postulated as the basis for many cerebral malformations including lissencephaly, cortical heterotopia, and double cortex. Recently, the genetic basis for some of these disorders has been identified. In this review, we highlight recent advances in our understanding of the molecular mechanisms of neuronal migration and its relationship to cerebral cortical development and neuronal migration disorders. This has allowed us to begin categorizing specific malformations based on their molecular etiology.

Animals↗
PubMed2005

Single translation--dual destination: mechanisms of dual protein targeting in eukaryotes.

It is well documented that single eukaryotic genes can give rise to proteins that are localized to several subcellular locations. This is achieved at the level of transcription, splicing and translation, and results in two or more translation products that either harbour or lack specific targeting signals. Nevertheless, the possibility of dual targeting of a single translation product has recently emerged. Here, we review cases of such dual targeting with emphasis on the mechanisms through which these phenomena occur. Proteins that harbour one signal, two separate signals or an overlapping ambiguous signal may follow dual distribution in the cell. The mechanism of dual targeting is driven by the competition or promiscuity of various molecular events. Protein folding, post-translational modification and protein-protein interaction are key players in this phenomenon.

Animals↗
PubMed2002

Cadets and nursing students: same destination - different route.

BACKGROUND: In response to the policy initiatives in England to secure recruitment and retention in the nursing and midwifery professions, strategies to improve and extend access to preregistration education and training in England have been developed. The relatively recent development of modern cadet schemes is an example of such a strategy. Despite the increasing interest in and proliferation of cadet schemes, there is as yet little evidence for their effectiveness. Reporting on an evaluation of a scheme in England, this paper makes some contribution to this evidence. AIMS AND OBJECTIVES: The project explored former nurse cadets' experiences of the cadet scheme 9 months after their transition to nurse education. The aims of the project were to evaluate the extent to which former cadets and university staff considered the scheme to prepare students effectively for access to university nurse education. METHODS: The first cohort of former cadets entered nurse education in September 2000. After 9 months they were invited to contribute to an evaluation of the cadet scheme and their present experience. The evaluation consisted of a structured questionnaire sent to all the former cadets, a focus group interview with the former cadets, informal discussions with university staff and brief documentary analysis. CONCLUSION: Tensions were apparent between the worlds of education and clinical practice: the cadets felt better prepared clinically than academically and found an element of repetition in the nursing programme. They valued their preparation, which they felt put them at an advantage over other nursing students. However, some of them experienced difficulties in the transition to higher education and further review is therefore required to establish the success of cadet schemes.

Adolescent↗
PubMed1999

A Drosophila gene encoding multiple splice variants of Kazal-type serine protease inhibitor-like proteins with potential destinations of mitochondria, cytosol and the secretory pathway.

A Drosophila gene (KAZ1), mapped to cytological position 61A1-2 on chromosome 3, has been cloned and found to encode multiple splice variants of Kazal-type serine protease inhibitor-like proteins. KAZ1 consists of five exons and four alternatively retained introns to produce six transcripts of type AB, C1, C2, C3, D and E. The AB transcript contains two ORFs, of which the upstream one produces a polypeptide alpha, which has a mitochondrial sorting signal. Localization to mitochondria was confirmed by expression in COS1 cells. The downstream ORF is shared partially with type C1, C2, C3, D and E transcripts and produces polypeptides beta, gamma, delta and epsilon when expressed in Drosophila cells. Type C1, C2 and C3 transcripts differ only in the 5'-noncoding sequence and thus all produce type gamma. Polypeptides gamma and epsilon have a signal sequence at their N-termini and are secreted into the medium while beta and delta lack this sequence and remain in the cytoplasm. Isoforms beta and epsilon share a common C-terminal sequence distinct from that shared by polypeptides gamma and delta. The N-terminal sequences of isoforms beta to epsilon contain a PEST region which could induce rapid intracellular degradation of isoforms beta and delta. Sequence analysis of the Kazal-type domain suggests a similar folding pattern as observed for rhodniin and SPARC/BM-40. Northern analysis and in situ hybridization showed that the type C3 transcript is predominant and the expression is highest in midgut at larval stage.

Amino Acid Sequence↗
PubMed2002

Travellers in many guises: the origins and destinations of dendritic cells.

The migratory behaviour of dendritic cells (DC) is tightly linked to their differentiation state. Precursor DC constitutively repopulate normal tissues from the bloodstream, and are recruited in elevated numbers to sites of inflammation. Whilst maturing in response to antigenic stimulation, DC acquire the capability to enter lymph nodes via afferent lymphatic vessels, thus facilitating their presentation of antigen to naïve T cells. Peripheral blood monocytes constitute a second DC precursor population, which during an inflammatory response are recruited to the affected site where some differentiate into functional DC. The availability of separate DC precursor populations is thought to be significant for the character, amplification and perpetuation of the resultant immune response. In addition, the balance between steady-state trafficking of incompletely activated DC bearing self-antigens from the periphery, and the migration of fully mature DC from inflammatory sites into lymph nodes might have profound effects upon tolerance induction and activation of T cells, respectively.

Animals↗
PubMed1991

Ultrasound findings in gestations destined for unanticipated fetal demise.

There are few reports of ultrasound findings in the second and third trimesters preceding intrauterine fetal demise. To describe these findings, the ultrasound assessments of 36 structurally normal singleton fetuses with subsequent intrauterine fetal demise were compared to gestational age-matched controls. Compared to controls, it was found that biparietal diameter, head circumference, femur length and estimated fetal weight were all decreased, abnormalities of amniotic fluid volume were more frequent, but the cephalic index was not different. Upon delivery, the group with subsequent intrauterine fetal demise was not found to have any major anomalies, but had a high incidence of abnormal umbilical cord position, abruptio placentae, chorioamnionitis and meconium aspiration.

Journal Article↗
PubMed2003

Discharge destination after dysvascular lower-limb amputations.

OBJECTIVE: To examine postacute care rehabilitation services use after dysvascular amputation. DESIGN: State-maintained hospital discharge data from the Maryland Health Services Cost Review Commission were analyzed. SETTING: Maryland statewide hospital discharge database. PARTICIPANTS: Persons discharged from nonfederal acute care hospitals from 1986 to 1997 with a procedure code for lower-limb amputation (ICD-9-CM code 84.12-.19), excluding toe amputations. Those persons with amputations due to trauma, bone malignancy, or congenital anomalies were excluded. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Postacute care service utilization. RESULTS: There were 16,759 discharges with an amputation procedure over this period. The average age was 69.3+/-14.3 years, and 51.9% were men. Black persons comprised 42.4% of the sample. Diabetes was present in 42.0%, and peripheral vascular disease was noted for 66.1% of amputees. Amputations were at the foot (19.4%), transtibial (38.1%), and transfemoral (42.4%) levels. The largest proportion (40.6%) of patients was discharged directly home after acute care, 37.4% went to a nursing home, 9.2% went home with home care, and 9.6% were discharged to an inpatient rehabilitation unit. From 1986 to 1997, there were downward trends in the rate of discharges directly home and corresponding upward trends in nursing home and inpatient rehabilitation dispositions. CONCLUSIONS: Inpatient rehabilitation use is infrequent after dysvascular amputation. Prospective studies are necessary to examine outcomes for persons receiving rehabilitation services in different care settings to define the optimal rehabilitation venue for functional restoration.

Aged↗
PubMed2001

The preterm prediction study: can low-risk women destined for spontaneous preterm birth be identified?

OBJECTIVE: Half of all preterm births occur in women without clinical risk factors. Our goal was to assess fetal fibronectin assay, Bishop score, and cervical ultrasonography as screening tests to predict which low-risk pregnancies will end in preterm birth. STUDY DESIGN: We performed a secondary analysis of data collected at 22 to 24 weeks' gestation from low-risk subjects enrolled in the Preterm Prediction Study, an observational study of risk factors for preterm birth conducted by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Analysis was limited to primigravid women and to women who did not have a history of preterm birth or spontaneous pregnancy loss at <20 weeks' gestation. Bishop score (> or =4), fetal fibronectin level (> or =50 ng/mL), and cervical length (< or =25 mm) at 24 weeks' gestation were evaluated alone and in sequence as tests to predict spontaneous delivery before 35 weeks' gestation. RESULTS: Of the 2929 subjects enrolled in the original study, 2197 (1207 primigravid women and 900 low-risk multiparous women) met criteria for this analysis. There were 64 spontaneous births before 35 weeks' gestation (3.04%). All three tests were significantly related to birth before 35 weeks' gestation (high Bishop score: relative risk, 3.6; 95% confidence interval, 2.1-6.3; fetal fibronectin detection: relative risk, 8.2; 95% confidence interval, 4.8-13.9; short cervical length: relative risk, 6.9; 95% confidence interval, 4.3-11.1). However, the sensitivities of the tests alone were low (23.4% for high Bishop score, 23.4% for fetal fibronectin detection, and 39.1% for short cervix), as were the sensitivities for Bishop score followed by cervical ultrasonography (14.1%) and fetal fibronectin assay followed by cervical scan (15.6%). CONCLUSION: In the setting of low-risk pregnancy, fetal fibronectin assay and cervical ultrasonography have low sensitivity for preterm birth before 35 weeks' gestation. Sequential screening with Bishop score or fetal fibronectin assay followed by cervical ultrasonography further decreased sensitivity to only 15% among low-risk women.

Cervix Uteri↗
PubMed2004

Cotranslational integration and initial sorting at the endoplasmic reticulum translocon of proteins destined for the inner nuclear membrane.

The current diffusion-retention model for protein trafficking to the inner nuclear membrane (INM) proposes that INM proteins diffuse laterally from the membrane of the endoplasmic reticulum into the INM and are then retained in the INM by binding to nuclear proteins or DNA. Because some data indicate that the sorting of baculovirus envelope proteins to the INM is protein-mediated, we have examined the early stages of INM protein integration and sorting by using photocrosslinking. Both viral and host INM-directed proteins were integrated cotranslationally through the endoplasmic reticulum translocon, and their nonrandom photocrosslinking to two translocon proteins, Sec61alpha and translocating chain-associated membrane protein (TRAM), revealed that the first transmembrane sequence (TMS) of each viral and host INM-directed protein occupied a very similar location within the translocon. Because few TMSs of non-INM-directed membrane proteins photocrosslink to TRAM, it seems that the INM-directed TMSs occupy different sites within the translocon than do non-INM-directed TMSs. The distinct proximities of translocon components to INM-directed TMSs strongly suggest that such TMSs are recognized and initially sorted within the translocon. Taken together, these data indicate that membrane protein sorting to the INM is an active process involving specific nonnuclear proteins.

Amino Acid Sequence↗