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1.
Sci Rep ; 10(1): 21335, 2020 12 07.
Article in English | MEDLINE | ID: mdl-33288785

ABSTRACT

While considered analogous to physical practice, the nature of imagery-based skill acquisition-specifically whether or not both effector independent and dependent encoding occurs through motor imagery-is not well understood. Here, motor imagery-based training was applied prior to or after physical practice-based training to probe the nature of imagery-based skill acquisition. Three groups of participants (N = 38) engaged in 10 days of training of a dart throwing task: 5 days of motor imagery prior to physical practice (MIP-PP), motor imagery following physical practice (PP-MIP), or physical practice only (PP-PP). Performance-related outcomes were assessed throughout. Brain activity was measured at three time points using fMRI (pre/mid/post-training; MIP-PP and PP-MIP groups). In contrast with physical practice, motor imagery led to changes in global versus specific aspects of the movement. Following 10 days of training, performance was greater when motor imagery preceded physical practice, although remained inferior to performance resulting from physical practice alone. Greater activation of regions that support effector dependent encoding was observed mid-, but not post-training for the PP-MIP group. Findings indicate that changes driven by motor imagery reflect effector independent encoding, providing new information regarding how motor imagery may be leveraged for skill acquisition.

2.
J Cogn Neurosci ; 32(8): 1590-1606, 2020 08.
Article in English | MEDLINE | ID: mdl-32420839

ABSTRACT

Despite its reported effectiveness for the acquisition of motor skills, we know little about how motor imagery (MI)-based brain activation and performance evolves when MI (the imagined performance of a motor task) is used to learn a complex motor skill compared to physical practice (PP). The current study examined changes in MI-related brain activity and performance driven by an equivalent bout of MI- or PP-based training. Participants engaged in 5 days of either MI or PP of a dart-throwing task. Brain activity (via fMRI) and performance-related outcomes were obtained using a pre/post/retention design. Relative to PP, MI-based training did not drive robust changes in brain activation and was inferior for realizing improvements in performance: Greater activation in regions critical to refining the motor program was observed in the PP versus MI group posttraining, and relative to those driven via PP, MI led only to marginal improvements in performance. Findings indicate that the modality of practice (i.e., MI vs. PP) used to learn a complex motor skill manifests as differences in both resultant patterns of brain activity and performance. Ultimately, by directly comparing brain activity and behavioral outcomes after equivalent training through MI versus PP, this work provides unique knowledge regarding the neural mechanisms underlying learning through MI.


Subject(s)
Imagination , Motor Skills , Brain/diagnostic imaging , Humans , Learning , Magnetic Resonance Imaging
3.
PLoS One ; 14(6): e0218423, 2019.
Article in English | MEDLINE | ID: mdl-31185044

ABSTRACT

[This corrects the article DOI: 10.1371/journal.pone.0174847.].

4.
Behav Brain Res ; 359: 135-142, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30392851

ABSTRACT

Sensory feedback has traditionally been considered critical for motor learning. While it has been shown that motor learning can occur in the absence of visual or somatosensory feedback, it is thought that at least one must be present. This assumption contrasts with literature demonstrating that motor imagery (MI) - the mental rehearsal of a movement - is capable of driving motor learning even though the lack of actual execution precludes sensory feedback related to movement. However, studies of MI typically employ simple tasks that do not require improvements in motor execution per se, suggesting that MI might improve task performance primarily through perceptual mechanisms. To avoid this limitation, we designed a novel motor task requiring the repeated execution of unfamiliar kinematic trajectories where learning was assessed through changes in the speed-accuracy function (SAF) across five sessions. General task performance was controlled for by assessing performance on randomly generated trajectories. Groups included physical practice (PP; with and without added visual feedback), MI, and perceptual control (PC), the latter of which only observed the trajectories. All groups performed physically on the final session. Upon the final session, the MI group performed better than the PC group, and better than initial session PP performance. These results suggest that motor learning occurred in the MI group despite the lack of sensory feedback related to the movement, and that this learning was not simply the result of perceptual learning. Our results question long-standing assumptions about MI based learning and the necessity of feedback in motor learning generally.


Subject(s)
Feedback, Sensory , Learning , Motor Skills , Movement , Biomechanical Phenomena , Electromyography , Female , Humans , Male , Motor Skills/physiology , Movement/physiology , Muscle, Skeletal/physiology , Upper Extremity/physiology , Visual Perception , Young Adult
5.
Tech Coloproctol ; 22(9): 649-655, 2018 09.
Article in English | MEDLINE | ID: mdl-30255213

ABSTRACT

Achieving a high-quality total mesorectal excision (TME) resection specimen is a central tenet of curative rectal cancer management. However, operating at the caudal extremity of the pelvis is inherently challenging and a number of patient- and tumour-related factors may increase the risk of obtaining a poor TME specimen and positive resection margins. Transanal TME (TaTME) is an advanced surgical technique developed to overcome the limitations in pelvic exposure and instrumentation of transabdominal surgery. This up-to-date narrative review describes the evolution of TME surgery, the indications for TaTME, current published outcomes, its limitations and future developments.


Subject(s)
Rectal Neoplasms/surgery , Transanal Endoscopic Surgery/adverse effects , Transanal Endoscopic Surgery/methods , Humans , Transanal Endoscopic Surgery/education , Treatment Outcome
6.
ANZ J Surg ; 88(9): 831-835, 2018 09.
Article in English | MEDLINE | ID: mdl-30069998

ABSTRACT

Today, colorectal surgeons globally are practicing in an exciting era where surgical technologies are constantly emerging. Most of these cutting-edge technologies are readily available in Australia and New Zealand at present. Thus the 'modern surgeon' should always be defined by this open-minded attitude towards these new and emerging surgical technologies. This review article highlights current modalities that we have been using in our north-Brisbane public and private hospitals for cases predicted to be technically challenging using minimally invasive approaches for most of them. We examined the current evidence regarding the following modalities and critiqued their use in clinical practice: lighted ureteric stents, minimally invasive surgery approaches of laparoscopy and robotic surgery, pressure barrier insufflation devices, 3D camera systems, hand-assist device ports and indocyanine green dye fluorescence angiography. The objective of this review paper is to alert colorectal surgeons to new surgical technologies available to them, to encourage colorectal surgeons' familiarization with these many technologies, and to support evidence-based consideration for the clinical use of such. These technologies should be supplemental aides to the safe, oncologically adequate and efficient operation that they already routinely perform.


Subject(s)
Colorectal Neoplasms/surgery , Colorectal Surgery/methods , Laparoscopy/trends , Surgeons/education , Australia/epidemiology , Evidence-Based Medicine , Hand-Assisted Laparoscopy/methods , Humans , Male , Minimally Invasive Surgical Procedures/methods , New Zealand/epidemiology , Robotic Surgical Procedures/methods , Surgeons/psychology
7.
Colorectal Dis ; 2017 Dec 11.
Article in English | MEDLINE | ID: mdl-29227015

ABSTRACT

Anastomotic leaks are a dreaded complication of all colorectal surgery with the main factors contributing to it being tension on the anastomosis, intra-abdominal or systemic sepsis, distal obstruction, inadequate blood supply and improper surgical techniques. The leak rate of left-sided high colorectal resections can have a clinically significant leak rate from as low as 1-5% in high anterior resections to 7.9% in low anastomoses. This article is protected by copyright. All rights reserved.

8.
Int J Colorectal Dis ; 32(7): 1061-1064, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28432443

ABSTRACT

BACKGROUND AND AIMS: Staging of colorectal cancer often fails to discriminate outcomes of patients with morphologically similar tumours that exhibit different clinical behaviours. Data from several studies suggest that the gastrin family of growth factors potentiates colorectal cancer tumourigenesis. The aim of this study was to investigate whether progastrin expression may predict clinical outcome in colorectal cancer. METHODS: Patients with colorectal adenocarcinoma of identical depth of invasion who had not received neoadjuvant therapy were included. The patients either had stage IIa disease with greater than 3-year disease-free survival without adjuvant therapy or stage IV disease with liver metastases on staging CT. Progastrin expression in tumour sections was scored with reference to the intensity and area of immunohistochemical staining. RESULTS: Progastrin expression by stage IV tumours was significantly greater than stage IIa tumours with mean progastrin immunopositivity scores of 2.1 ± 0.2 versus 0.5 ± 0.2, respectively (P < 0.001). CONCLUSIONS: This is the first study to show that progastrin expression may be predictive of aggressive tumour behaviour in patients with colorectal cancer and supports its clinical relevance and potential use as a biomarker.


Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Gastrins/metabolism , Liver Neoplasms/secondary , Protein Precursors/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Aged , Colorectal Neoplasms/pathology , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging
9.
PLoS One ; 12(4): e0174847, 2017.
Article in English | MEDLINE | ID: mdl-28399158

ABSTRACT

Mild traumatic brain injury (mTBI), or concussion, is the most common type of traumatic brain injury. With mTBI comes symptoms that include headaches, fatigue, depression, anxiety and irritability, as well as impaired cognitive function. Symptom resolution is thought to occur within 3 months post-injury, with the exception of a small percentage of individuals who are said to experience persistent post-concussion syndrome. The number of individuals who experience persistent symptoms appears to be low despite clear evidence of longer-term pathophysiological changes resulting from mTBI. In light of the incongruency between these longer-term changes in brain pathology and the number of individuals with longer-term mTBI-related symptoms, particularly impaired cognitive function, we performed a scoping review of the literature that behaviourally assessed short- and long-term cognitive function in individuals with a single mTBI, with the goal of identifying the impact of a single concussion on cognitive function in the chronic stage post-injury. CINAHL, Embase, and Medline/Ovid were searched July 2015 for studies related to concussion and cognitive impairment. Data relating to the presence/absence of cognitive impairment were extracted from 45 studies meeting our inclusion criteria. Results indicate that, in contrast to the prevailing view that most symptoms of concussion are resolved within 3 months post-injury, approximately half of individuals with a single mTBI demonstrate long-term cognitive impairment. Study limitations notwithstanding, these findings highlight the need to carefully examine the long-term implications of a single mTBI.


Subject(s)
Brain Concussion/complications , Brain Concussion/epidemiology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Brain Concussion/psychology , Chronic Disease , Humans
10.
Behav Neurosci ; 130(2): 252-60, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26854741

ABSTRACT

Motor imagery (MI), the mental rehearsal of movement, is an effective means for acquiring a novel skill, even in the absence of physical practice (PP). The nature of this learning, be it perceptual, motor, or both, is not well understood. Understanding the mechanisms underlying MI-based skill acquisition has implications for its use in numerous disciplines, including informing best practices regarding its use. Here we used an implicit sequence learning (ISL) task to probe whether MI-based skill acquisition can be attributed to perceptual or motor learning. Participants (n = 60) randomized to 4 groups were trained through MI or PP, and were then tested in either perceptual (altering the sensory cue) or motor (switching the hand) transfer conditions. Control participants (n = 42) that did not perform a transfer condition were utilized from previous work. Learning was quantified through effect sizes for reaction time (RT) differences between implicit and random sequences. Generally, PP-based training led to lower RTs compared with MI-based training for implicit and random sequences. All groups demonstrated learning (p < .05), the magnitude of which was reduced by transfer conditions relative to controls. For MI-based training perceptual transfer disrupted performance more than for PP. Motor transfer disrupted performance equally for MI- and PP-based training. Our results suggest that MI-based training relies on both perceptual and motor learning, while PP-based training relies more on motor processes. These results reveal details regarding the mechanisms underlying MI, and inform its use as a modality for skill acquisition. (PsycINFO Database Record


Subject(s)
Imagination/physiology , Motor Skills/physiology , Adult , Animals , Female , Humans , Learning , Male , Neuropsychological Tests , Psychomotor Performance/physiology , Transfer, Psychology/physiology , Young Adult
11.
J Vis ; 16(3): 25, 2016.
Article in English | MEDLINE | ID: mdl-26891832

ABSTRACT

In the size-weight illusion (SWI), small objects feel heavier than larger objects of the same mass. This effect is typically thought to be a consequence of the lifter's expectation that the large object will outweigh the small object, because objects of the same type typically get heavier as they get larger. Here, we show that this perceptual effect can occur across object category, where there are no strong expectations about the correspondence between size and mass. One group of participants lifted same-colored large and small cubes with the same mass as one another, while another group lifted differently-colored large and small cubes with the same mass as one another. The group who lifted the same-colored cubes experienced a robust SWI and initially lifted the large object with more force than the small object. By contrast, the group who lifted the different-colored objects did so with equal initial forces on the first trial, but experienced just as strong an illusion as those who lifted the same-colored objects. These results demonstrate that color cues can selectively influence the application of fingertip force rates while not impacting at all upon the lifter's perception of object weight, highlighting a stark dissociation in how prior information affects perception and action.


Subject(s)
Illusions/physiology , Size Perception/physiology , Weight Perception/physiology , Color , Cues , Female , Humans , Male , Probability , Young Adult
12.
J Exp Psychol Hum Percept Perform ; 42(2): 257-65, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26389615

ABSTRACT

Motor learning depends upon plasticity in neural networks involved in the planning and execution of movement. Physical practice (PP) is the primary means of motor learning, but it can be augmented with nonphysical forms of practice including motor imagery (MI)-the mental rehearsal of movement. It is unknown if MI alone, without prior PP of a movement, can produce robust learning. Here the authors used an implicit sequence learning task to explore motor learning via MI alone or PP. Participants underwent implicit sequence learning training via MI (n = 31) or PP (n = 33). Posttraining reaction time was faster for implicit versus random sequences for both the MI group (M = 583 ± 84 ms; 632 ± 86 ms, d = 0.59) and PP group (M = 532 ± 73 ms; 589 ± 70 ms, d = 0.80), demonstrating that MI without PP facilitated skill acquisition. Relative to MI alone, PP led to reduced reaction time for both random (d = 0.65) and implicit sequences (d = 0.55) consistent with a nonspecific motor benefit favoring PP over MI. These results have broad implication for theories of MI and support the use of MI as a form of practice to acquire implicit motor skills. (PsycINFO Database Record


Subject(s)
Imagination/physiology , Learning/physiology , Motor Activity/physiology , Motor Skills/physiology , Practice, Psychological , Adult , Female , Humans , Male , Young Adult
13.
Exp Brain Res ; 234(4): 955-62, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26680770

ABSTRACT

Reports of spatial interactions between current and upcoming elements in a movement sequence could be due to intentional planning of a "global" action sequence (i.e., strategic effects), or to unintentional motor planning arising from merely paying attention to upcoming target objects (i.e., interference effects). The purpose of this experiment was to determine whether paying attention to an upcoming target object could induce kinematic changes in a current grasping action when there is no strategic advantage associated with such changes. Specifically, participants grasped a rectangular target object in the presence of a second rectangular object that was either ignored, or was the target of a subsequent grasping or perceptual judgment task. Peak grip aperture during the primary grasping action was assessed in relation to the size of the second rectangle. The results revealed an effect of the second rectangle's size only when it was the target of a subsequent perceptual judgment task. This result calls into question the assumption that interactions between current and subsequent elements of an action sequence are necessarily due to strategic movement planning processes and might instead arise from interference arising from merely paying attention to nontarget objects.


Subject(s)
Hand Strength/physiology , Psychomotor Performance/physiology , Reaction Time/physiology , Visual Perception/physiology , Female , Humans , Male , Photic Stimulation/methods , Young Adult
14.
Can J Occup Ther ; 82(4): 224-34, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26502017

ABSTRACT

BACKGROUND: Occupational therapists routinely use observation for evaluation, intervention planning, and prediction of a client's occupational performance and/or safety within the environment. Perception of safety contributes to the decision-making process for discharge or placement recommendations. PURPOSE: The purpose of this study was to determine if differences exist in safety ratings and eye movements between occupational therapists and nontrained matched individuals while viewing domain-specific versus non-domain-specific images. METHOD: Ten licensed occupational therapists and 10 age-, gender-, and education level-matched participants completed this eye-tracking study. FINDINGS: For all image exposure durations, occupational therapists had more polarized safety ratings for stroke-related image content but little evidence of differences in eye movements between groups. Eye movement group differences did not emerge in the regions of interest identified by an independent expert panel. IMPLICATIONS: The results point to a complex relationship between decision making and observational behaviour in occupational assessment and highlight the need to look beyond image features.


Subject(s)
Attention , Occupational Therapy , Patient Safety , Visual Perception , Adult , Case-Control Studies , Eye Movement Measurements , Eye Movements , Female , Humans , Male , Middle Aged , Observer Variation , Stroke Rehabilitation
15.
Exp Brain Res ; 233(11): 3283-90, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26259747

ABSTRACT

We have shown that the latency to initiate a reaching movement is increased if its direction is the same as a previous movement compared to movements that differ by 90° or 180° (Cowper-Smith and Westwood in Atten Percept Psychophys 75:1914-1922, 2013). An influential study (Taylor and Klein in J Exp Psychol Hum Percept Perform 26:1639-1656, 2000), however, reported the opposite spatial pattern for manual keypress responses: repeated responses on the same side had reduced reaction time compared to responses on opposite sides. In order to determine whether there are fundamental differences in the patterns of spatial interactions between button-pressing responses and reaching movements, we compared both types of manual responses using common methods. Reaching movements and manual keypress responses were performed in separate blocks of trials using consecutive central arrow stimuli that directed participants to respond to left or right targets. Reaction times were greater for manual responses made to the same target as a previous response (M = 390 ms) as compared to the opposite target (M = 365 ms; similarity main effect: p < 0.001) regardless of whether the response was a reaching movement or a keypress response. This finding is broadly consistent with an inhibitory mechanism operating at the level of motor output that discourages movements that achieve the same spatial goal as a recent action.


Subject(s)
Attention/physiology , Inhibition, Psychological , Psychomotor Performance/physiology , Space Perception/physiology , Analysis of Variance , Female , Humans , Male , Photic Stimulation , Reaction Time/physiology , Time Factors , Young Adult
16.
PLoS One ; 10(4): e0123666, 2015.
Article in English | MEDLINE | ID: mdl-25881269

ABSTRACT

Reaction times to targets presented in the same location as a preceding cue are greater than those to targets presented opposite the cued location. This observation can be explained as a result of inhibition at the attended location (IOR), or as facilitation at the location opposite the cue (opposite facilitation effect or OFE). Past research has demonstrated that IOR is observed reliably, whereas OFE is observed only occasionally. The present series of four experiments allows us to determine whether or not OFE can be explained by eye movements as suggested by previous authors. Participants' eye movements were monitored as they were presented with an array of four placeholders aligned with the four cardinal axes. Exogenous cues and targets were presented successively. Participants (N=37) completed either: i.) cue-manual and cue-saccade experiments, ignoring the cue and then responding with a keypress or saccade, respectively, or ii.) manual-manual and saccade-saccade experiments, responding to both the cue and the target with a keypress or saccade respectively. Results demonstrated a reliable IOR effect in each of the four experiments (reaction time greater for same versus adjacent and opposite cue-target trials). None of the four experiments demonstrated evidence of an OFE (reaction times were not significantly lower for opposite versus adjacent cue-target trials). These results are inconsistent with a momentum-based account of cue-target task performance, and furthermore suggest that the OFE cannot be attributed to occasional eye movements to the cue and/or target in previous studies.


Subject(s)
Ocular Physiological Phenomena , Reaction Time , Adult , Attention , Cues , Female , Humans , Male , Nontherapeutic Human Experimentation , Saccades/physiology
17.
Exp Brain Res ; 233(7): 2029-40, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25869741

ABSTRACT

When an individual grasps a physical object, the visuomotor system is able to specify grip aperture via absolute visual information. In contrast, grasping to a location previously occupied by an object (i.e., pantomime-grasping) results in the specification of grip aperture via relative visual information. The basis for the dissociable visual codes is thought to reflect that pantomime-grasping is a perception-based task. It is, however, important to recognize that grasping a physical object and pantomime-grasping differ not only in terms of their visuospatial properties but also with respect to the availability of haptic feedback: Grasping a physical object provides haptic cues derived from touching the object, whereas no such feedback is available in a traditional pantomime-grasping task. As such, we examined whether haptic feedback influences the information supporting a pantomime-grasp performed after a 1000-ms visual delay. Participants completed responses in each of the three tasks: (1) grasping a physical object, (2) traditional pantomime-grasping wherein the to-be-grasped object was removed from the grasping environment and (3) pantomime-grasping wherein the experimenter placed the object between participants' thumb and forefinger once they had completed their response (i.e., pantomime-grasping with haptic feedback). Just-noticeable-difference (JND) scores were computed to determine whether responses adhered to or violated the psychophysical (i.e., relative) principles of Weber's law. JNDs for the traditional pantomime-grasping task adhered to Weber's law, whereas JNDs for grasping a physical object and for pantomime-grasping with haptic feedback violated the law. Thus, we propose that convergent visual and haptic cues support the absolute specification of object size in a pantomime-grasping task. Furthermore, our results highlight the important role of multisensory cue integration in a target-defined grasping task.


Subject(s)
Feedback, Sensory/physiology , Hand Strength/physiology , Psychomotor Performance/physiology , Touch Perception/physiology , Touch/physiology , Adolescent , Adult , Analysis of Variance , Biomechanical Phenomena , Female , Humans , Male , Memory , Psychophysics , Young Adult
18.
Front Hum Neurosci ; 8: 872, 2014.
Article in English | MEDLINE | ID: mdl-25389401

ABSTRACT

One way to explore how prior sensory and motor events impact eye movements is to ask someone to look to targets located about a central point, returning gaze to the central point after each eye movement. Concerned about the contribution of this return to center movement, Anderson et al. (2008) used a sequential saccade paradigm in which participants made a continuous series of saccades to peripheral targets that appeared to the left or right of the currently fixated location in a random sequence (the next eye movement began from the last target location). Examining the effects of previous saccades (n-x) on current saccade latency (n), they found that saccadic reaction times (RT) were reduced when the direction of the current saccade matched that of a preceding saccade (e.g., two left saccades), even when the two saccades in question were separated by multiple saccades in any direction. We examined if this pattern extends to conditions in which targets appear inside continuously marked locations that provide stable visual features (i.e., target "placeholders") and when saccades are prompted by central arrows. Participants completed 3 conditions: peripheral targets (PT; continuous, sequential saccades to peripherally presented targets) without placeholders; PT with placeholders; and centrally presented arrows (CA; left or right pointing arrows at the currently fixated location instructing participants to saccade to the left or right). We found reduced saccadic RT when the immediately preceding saccade (n-1) was in the same (vs. opposite) direction in the PT without placeholders and CA conditions. This effect varied when considering the effect of the previous 2-5 (n-x) saccades on current saccade latency (n). The effects of previous eye movements on current saccade latency may be determined by multiple, time-varying mechanisms related to sensory (i.e., retinotopic location), motor (i.e., saccade direction), and environmental (i.e., persistent visual objects) factors.

19.
Biochim Biophys Acta ; 1843(11): 2471-80, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24998603

ABSTRACT

AIM: Gastrins act as growth factors for the normal and neoplastic colorectal mucosa. The aim of this study was to determine the role of gastrins in the response of human colorectal cancer (CRC) cells to hypoxia in vitro and in vivo. METHODS: Expression of the gastrin gene in the human CRC cell line LoVo was examined under normoxia and hypoxia by quantitative PCR and by radioimmunoassay. Gastrin expression was knocked down with shRNA, and the effect on cell proliferation was measured by cell counting, on cell apoptosis by annexin V staining, and on cell migration by Boyden chamber assay. The effect of gastrin knockdown on tumourigenesis in mouse xenografts was analysed by measurement of tumour volumes and weights, and by immunohistochemistry. RESULTS: Gastrin gene expression in LoVo cells was stimulated by hypoxia via binding of hypoxia-inducible factor-1α to the gastrin promoter. The viability of gastrin knockdown cells exposed to hypoxia (1% O2) in vitro was diminished because of loss of resistance against hypoxia-induced apoptosis, and the effect was partly reversed by treatment with non-amidated, but not amidated, gastrin. Conditioned medium from control LoVo cells under hypoxia simulated proliferation but not migration, and the effect was blocked by an inhibitor of non-amidated gastrins, but not by an inhibitor of amidated gastrins. In xenografts in mice exposed to hypoxia (10% O2) for 21days, tumour necrosis was significantly increased by knocking down gastrin expression. CONCLUSION: These results provide evidence that non-amidated gastrins are involved in the adaptation of CRCs to hypoxic microenvironments through increasing resistance to apoptosis.

20.
Biochemistry ; 52(35): 6108-13, 2013 Sep 03.
Article in English | MEDLINE | ID: mdl-23919461

ABSTRACT

The Bam machine assembles ß-barrel membrane proteins into the outer membranes of Gram-negative bacteria. The central component of the Bam complex, BamA, is a ß-barrel that is conserved in prokaryotes and eukaryotes. We have previously reported an in vitro assay for studying the assembly of ß-barrel proteins by the Bam complex and now apply this assay to identify the specific components that are required for BamA assembly. We establish that BamB and BamD, two lipoprotein components of the complex, bind to the unfolded BamA substrate and are sufficient to accelerate its assembly into the membrane.


Subject(s)
Bacterial Outer Membrane Proteins/metabolism , Escherichia coli Proteins/metabolism , Lipoproteins/metabolism , Chromatography, Affinity , Escherichia coli/metabolism , In Vitro Techniques , Protein Folding
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