Brca1 inactivation induces p27Kip1-dependent cell cycle arrest and delayed development in the mouse mammary gland

One common characteristic of breast cancers arising in carriers of the predisposition gene BRCA1 is a loss of expression of the CDK inhibitor p27(Kip1) (p27), suggesting that p27 interacts epistatically with BRCA1. To investigate this relationship, we examined expression of p27 in mice expressing a dominant negative allele of Brca1 (MMTV-trBr) in the mammary gland. While these mice rarely develop tumors, they showed a 50% increase in p27 protein and a delay in mammary gland development associated with reduced proliferation. In contrast, on a p27 heterozygote background, MMTV-trBrca1 mice showed an increase in S phase cells, and normal mammary development. p27 was the only protein in the cyclin cyclin-dependent kinase network to show altered expression, suggesting that it may be a central mediator of cell cycle arrest in response to loss of function of BRCA1. Furthermore, in human mammary epithelial MCF7 cells expressing BRCA1-specific RNAi and in the BRCA1-deficient human tumor cell line HCC1937, p27 is elevated at the mRNA level compared to cells expressing wild-type BRCA1. We hypothesize that disruption of BRCA1 induces an increase in p27 that inhibits proliferation. Accordingly, reduction in p27 expression leads to enhancement of cellular proliferation in the absence of BRCA1.

Functionalized macrocycles from functionalized tetra-amines: Pendent-arm macrocycles derived from dichloropivalic acid

Reaction between ethane-1,2-diamine and 3,3'-dichloropivalic acid results in different, isomeric tetra-amine derivatives, one a tetraamino carboxylic acid and the other a carboxamidotriamino alcohol, depending upon reaction conditions, Intended conversion of the Cu(II) complex of the former to a cyclam-like macrocycle through reaction with nitroethane and formaldehyde results in isolation of derivatives of both the former and the latter. This can be rationalized by assuming the intermediacy of an azetidinone, a species similar to that seen in simpler reactions of dichloropivalates. A single reaction thereby provides pendent-arm macrocycles where one has an electrophilic and the other a nucleophilic substituent. Parallel chemistry is not seen in the reaction between propane-1,3-diamine and 3,3'-dichloropivalate.

Do you know where your arm is if you think your head has moved?

Reproduction of a previously presented elbow position is affected by changes in head position. As movement of the head is associated with local biomechanical changes, the aim of the present study was to determine if illusory changes in head position could induce similar effects on the reproduction of elbow position. Galvanic vestibular stimulation (GVS) was applied to healthy subjects in supine lying. The stimulus was applied during the presentation of an elbow position, which the subject then reproduced without stimulation. In the first study, 13 subjects received 1.5 mA stimuli, which caused postural sway in standing, confirming that the firing of vestibular afferents was affected, but no illusory changes in head position were reported. In the second study, 13 subjects received 2.0-3.0 mA GVS. Six out of 13 subjects reported consistent illusory changes in head position, away from the side of the anode. In these subjects, anode right stimulation induced illusory left lateral flexion and elbow joint position error towards extension (p=0.03), while anode left tended to have the opposite effect (p=0.16). The GVS had no effect on error in subjects who did not experience illusory head movement with either 1.5 mA stimulus (p=0.8) or 2.0-3.0 mA stimulus (p=0.7). This study demonstrates that the accuracy of elbow repositioning is affected by illusory changes in head position. These results support the hypothesis that the perceived position of proximal body segments is used in the planning and performance of accurate upper limb movements.

Influence of predominant patterns of coordination on the exploitation of interaction torques in a two-joint rhythmic arm movement

In this study we investigate the coordination between rhythmic flexion-extension (FE) and supination-pronation (SP) movements at the elbow joint-complex, while manipulating the intersegmental dynamics by means of a 2-degrees of freedom (df) robot arm. We hypothesized that constraints imposed by the structure of the neuromuscular-skeletal system would (1) result in predominant pattern(s) of coordination in the absence of interaction torques and (2) influence the capabilities of participants to exploit artificially induced interaction torques. Two experiments were conducted in which different conditions of interaction torques were applied on the SP-axis as a function of FE movements. These conditions promoted different patterns of coordination between the 2-df. Control trials conducted in the absence of interaction torques revealed that both the in-phase (supination synchronized with flexion) and the anti-phase (pronation synchronized with flexion) patterns were spontaneously established by participants. The predominance of these patterns of coordination is explained in terms of the mechanical action of bi-articular muscles acting at the elbow joint-complex, and in terms of the reflexes that link the activity of the muscles involved. Results obtained in the different conditions of interaction torques revealed that those neuromuscular-skeletal constraints either impede or favor the exploitation of intersegmental dynamics depending on the context. Interaction torques were indeed found to be exploited to a greater extent in conditions in which the profiles of interaction torques favored one of the two predominant patterns of coordination (i.e., in-phase or anti-phase) as opposed to other patterns of coordination (e.g., 90 degrees or 270 degrees). Those results are discussed in relation to recent studies reporting exploitation of interaction torques in the context of rhythmic movements.

Neuromuscular-skeletal origins of predominant patterns of coordination in a rhythmic two-joint arm movement

The authors tested for predominant patterns of coordination in the combination of rhythmic flexion-extension (FE) and supination-pronation (SP) at the elbow-joint complex. Participants (N = 10) spontaneously established in-phase (supination synchronized with flexion) and antiphase (pronation synchronized with flexion) patterns. In addition, the authors used a motorized robot arm to generate involuntary SP movements with different phase relations with respect to voluntary FE. The involuntarily induced in-phase pattern was accentuated and was more consistent than other patterns. That result provides evidence that the predominance of the in-phase pattern originates in the influence of neuro-muscular-skeletal constraints rather than in a preference dictated by perceptual-cognitive factors implicated in voluntary control. Neuromuscular-skeletal constraints involved in the predominance of the in-phase and the antiphase patterns are discussed.

Reliability and validity of arm volume measurements for assessment of lymphedema

Background and Purpose. Arm lymphedema following breast cancer In this study, we assessed the surgery is a continuing problem. reliability and validity of circumferential measurements and water displacement for measuring upper-limb volume. Subjects. Participants included subjects who had had breast cancer surgery, including axillary dissection-19 with and 22 without a diagnosis of arm lymphedema-and 25 control subjects. Methods. Two raters measured each subject by using circumferential tape measurements at specified distances from the fingertips and in relation to anatornic landmarks and by using water displacement. Interrater reliability was calculated by analysis of variance and multilevel modeling. Volumes from circumferential measurements were compared with those from water displacement by use of means and correlation coefficients, respectively. The standard error of measurement, minimum detectable change (MDC), and limits of agreement (LOA) for volumes also were calculated. Results. Arm volumes obtained with these methods had high reliability. Compared with volumes from water displacement, volumes from circumferential measurements had high validity, although these volumes were slightly larger. Expected differences between subjects with and without clinical lymphedema following breast cancer were found. The MDC of volumes or the error associated with a single measure for data based oil anatomic landmarks was lower than that based oil distance from fingertips. The mean LOA with water displacement were lower for data based on anatomic landmarks than for data based on distance from fingertips. Discussion and Conclusion. Volumes calculated from anatomic landmarks are reliable, valid, and more accurate than those obtained from circumferential measurements based on distance from fingertips.

Synthesis and aggregation behavior of four-arm star amphiphilic block copolymers in water

We report the first synthesis of amphiphilic four-arm star diblock copolymers consisting of styrene (STY) and acrylic acid (AA) made using reversible addition-fragmentation chain transfer (RAFT; Z group approach with no star-star coupling). The polymerization proceeded in an ideal living manner. The size of the poly(AA(132)-STYm)(4) stars in DMF were small and close to 7 nm, suggesting no star aggregation. Slow addition of water (pH = 6.8) to this mixture resulted in aggregates of 15 stars per micelle with core-shell morphology. Calculations showed that the polyAA blocks were slightly extended with a shell thickness of 15 nm. Treatment of these micelles with piperidine to cleave the block arms from the core resulted in little or no change on micelle size or morphology, but the polyAA shell thickness was close to 29 nm (33 nm is the maximum at full extension) suggesting a release of entropy when the arms are detached from the core molecule. In this work we showed through the use of star amphiphilic polymers that the micelle size, aggregation number, and morphology could be controlled.

Validation of the Action Research Arm Test using item response theory in patients after stroke

Objective: To validate the unidimensionality of the Action Research Arm Test (ARAT) using Mokken analysis and to examine whether scores of the ARAT can be transformed into interval scores using Rasch analysis. Subjects and methods: A total of 351 patients with stroke were recruited from 5 rehabilitation departments located in 4 regions of Taiwan. The 19-item ARAT was administered to all the subjects by a physical therapist. The data were analysed using item response theory by non-parametric Mokken analysis followed by Rasch analysis. Results: The results supported a unidimensional scale of the 19-item ARAT by Mokken analysis, with the scalability coefficient H = 0.95. Except for the item pinch ball bearing 3rd finger and thumb'', the remaining 18 items have a consistently hierarchical order along the upper extremity function's continuum. In contrast, the Rasch analysis, with a stepwise deletion of misfit items, showed that only 4 items (grasp ball'', grasp block 5 cm(3)'', grasp block 2.5 cm(3)'', and grip tube 1 cm(3)'') fit the Rasch rating scale model's expectations. Conclusion: Our findings indicated that the 19-item ARAT constituted a unidimensional construct measuring upper extremity function in stroke patients. However, the results did not support the premise that the raw sum scores of the ARAT can be transformed into interval Rasch scores. Thus, the raw sum scores of the ARAT can provide information only about order of patients on their upper extremity functional abilities, but not represent each patient's exact functioning.

Postural activity of the pelvic floor muscles is delayed during rapid arm movements in women with stress urinary incontinence

The aim of this study was to determine whether postural activity of the pelvic floor (PF) and abdominal muscles differs between continent and incontinent women during rapid arm movements that present a postural challenge to the trunk. A further aim was to study the effect of bladder filling. Electromyographic activity (EMG) of the PF, abdominal, erector spinae (ES), and deltoid muscles was recorded with surface electrodes. During rapid shoulder flexion and extension, PF EMG increased before that of the deltoid in continent women, but after the deltoid in incontinent women (p= 0.002). In many incontinent women, PF EMG decreased before the postural activation. Although delayed, postural PF EMG amplitude was greater in women with incontinence ( p= 0.010). In both groups, PF EMG decreased and abdominal and ES EMG increased when the bladder was moderately full. These findings would be expected to have negative consequences for continence and lumbopelvic stability in women with incontinence.