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PubMed1992

Adjacent zinc-finger motifs in multiple zinc-finger peptides from SWI5 form structurally independent, flexibly linked domains.

Peptides containing either one, two or three of the three zinc-finger motifs from the yeast transcription factor SWI5 have been prepared by expression in Escherichia coli. The DNA binding characteristics of these peptides were investigated, and a two-dimensional nuclear magnetic resonance (n.m.r.) study undertaken to establish the three-dimensional structures of the two-finger peptide. The peptide containing fingers 1 and 2 binds sequence specifically to two thirds of the DNA binding site recognized either by intact SWI5 or by the isolated three-finger peptide, and hence has the correct tertiary fold for DNA recognition. These results also establish the polarity of DNA binding, since the N-terminal two fingers of SWI5 bind to the 5' end of the DNA binding site. Mild proteolysis of the three-finger peptide using trypsin results in a small number of discrete products, which is consistent with the presence of three structured mini-domains. Nearly complete n.m.r. signal assignments were obtained for two peptides containing finger 2 alone or fingers 1 + 2. Comparison of two-dimensional spectra of these peptides and others clearly shows that the NOE enhancements and chemical shifts characteristic of each finger are quite insensitive to the presence or absence of neighbouring fingers. This clearly indicates that adjacent zinc-finger domains are structurally independent in these peptides from SWI5. However, there must be some steric limitations on the possible relative orientations of the fingers, and to establish limits for these a set of structures for the peptide containing fingers 1 + 2 was calculated using the YASAP simulated annealing protocol in conjunction with n.m.r.-based constraints. A more detailed description of the three-dimensional structures of finger 1 and finger 2, and their relationship to other previously determined structures of single zinc-fingers, is given in the accompanying paper.

Amino Acid Sequence↗
PubMed2003

Effect of simulated rock climbing finger postures on force sharing among the fingers.

OBJECTIVE: To study the forces applied by each finger in different joint postures simulating rock climbing gripping postures. DESIGN: Subjects in sitting posture applied fingertip forces perpendicular to horizontal force sensors in three different finger postures. BACKGROUND: Data provided by the literature indicate that middle and ring finger are commonly injured. However, no quantitative assessment of the forces applied by each finger related to the joint postures has been made. METHODS: Six elite rock climbers performed finger flexion in a single-finger task and a four-finger task. The tests were conducted in an extended posture, a curved posture (the joints belonging to the finger were flexed) and an intermediate posture (the joints were flexed, except the distal one which was fully extended). Each fingertip force was expressed in absolute value and in percentage of the maximal force capacity of the finger. RESULTS: The greater force was applied by the middle finger (20.8 N), whatever the posture. The relative involvement amounted to 105% for the ring finger in the curved posture. CONCLUSIONS: The great force applied by the middle finger and the great relative involvement of the ring finger in the curved posture seem to be the main factors of injuries of these fingers. RELEVANCE: The analysis of force sharing among the fingers during different joint postures mimicking rock climbing is essential to a better understanding of finger injuries.

Adult↗
PubMed1995

Contributions and co-ordination of individual fingers in multiple finger prehension.

The contributions and co-ordination of external finger grip forces were examined during a lifting task with a precision grip using multiple fingers. The subjects (n = 10) lifted a force transducer-equipped grip apparatus. Grip force from each of the five fingers was continuously measured under different object weight (200 g, 400 g and 800 g) and surface structure (plastic and sandpaper) conditions. The effect of five-, four-, and three-finger grip modes was also examined. It was found that variation of object weight or surface friction resulted in change of the total grip force magnitude; the largest change in finger force, was that for the index finger, followed by the middle, ring, and little fingers. Percentage contribution of static grip force to the total grip force for the index, middle, ring, and little fingers was 42.0%, 27.4%, 17.6% and 12.9%, respectively. These values were fairly constant for all object weight conditions, as well as for all surface friction conditions, suggesting that all individual finger force adjustments for light loads less than 800 g are controlled comprehensively simply by using a single common scaling value. A higher surface friction provided faster lifting initiation and required lesser grip force exertion, indicating advantageous effect of a non-slippery surface over a slippery surface. The results indicate that nearly 40% force reduction can be obtained when a non-slippery surface is used. Variation in grip mode changed the total grip force, i.e., the fewer the number of fingers, the greater the total grip force. The percent value of static grip force for the index, middle, and ring fingers in the four-finger grip mode was 42.7%, 32.5%, and 24.7%, respectively, and that for the index and middle fingers in the three-finger grip mode was 43.0% and 56.9%, respectively. Therefore, the grip mode was found to influence the force contributions of the middle and ring fingers, but not of the index finger.

Adolescent↗
PubMed1995

Finger systolic blood pressures: effects of cold provocation on the reference finger.

Finger systolic blood pressure measured after cold provocation and ischemia of a digit is used to assist in the diagnosis of vibration-induced white finger, VWF. A reduction in finger systolic blood pressure after cooling is assumed to indicate vascular dysfunction. The percentage pressure change observed in the tested finger is often corrected for whole body effects (systemic systolic pressure changes) according to the pressure change measured in a reference finger. The commonly used method of correction is based on assumptions as to the causes of any changes occurring in the reference finger. It is assumed that the reference finger is not differentially susceptible to the cold provocation of the test finger, arising from either close proximity to the cold provocation or from a vascular disorder in the reference finger. An experiment has been undertaken to investigate the repeatability, over three days, of measurements of the arm systolic pressures of both arms and the finger systolic pressures in air of four fingers of both hands. The systolic pressures of both arms and of four fingers of one hand were also measured whilst the fifth finger of the same hand was subjected to cold provocation at 10 degrees C. Twelve healthy male subjects were rested in a supine position for 15 minutes in a room at 21-24 degrees C before measurements were taken. Finger systolic blood pressures were recorded using strain gauge plethysmography. The results show that the systolic blood pressure measurements were generally repeatable, but differed with measurement location. Cold provocation of the test finger had little consistent effect on the systolic pressures measured at other locations. The results are interpreted with regard to the correction of finger systolic pressure using a reference measurement.

Adult↗
PubMed1993

A cortical slow potential is larger before an isolated movement of a single finger than simultaneous movement of two fingers.

Movement-related cortical potentials (MRCPs) preceding voluntary, self-paced, simultaneous extension of the middle and index fingers (two finger movement) were compared with those preceding extension of the index or middle finger alone (single finger movement) of the right hand in 7 right-handed normal subjects. It was meant to double the number of muscles involved in the two finger movement as compared with the single finger movement and to activate only the motor cortex involving the movement of distal joints. The NS' (negative slope) amplitude with the isolated middle finger movement was significantly larger at the precentral area contralateral to the movement as compared with the two finger movement. The NS' amplitude with the index finger movement was also larger than that with the two finger movement at the contralateral precentral area, but the difference was not significant. It is postulated that greater activation of the primary hand sensorimotor area (HSMA) contralateral to the movement might be necessary for the isolated movement of a single finger than for the two finger movement, although a smaller area of HSMA is expected to be activated in the former than in the latter. The NS' may be related to central motor control processes independent of muscle mass activated. As the single finger movement is considered to be more discrete and fine as compared with the simultaneous two finger movement, it is concluded that the HSMA plays an especially important role in discrete and fine finger movement.

Adult↗
PubMed2000

Phantom finger phenomena and the effects of toe-to-finger transplantation.

Phantom finger phenomena and the effects of toe-to-finger transplantation were studied in 76 patients who had had traumatic finger amputation. Phantom finger phenomena were observed in 48 (63%) patients with the presence of phantom finger only in 30, phantom finger with sensation in nine, and phantom finger with motion also in nine. After toe transplantation, phantom finger phenomena disappeared immediately in about half of the transplanted fingers that had phantom phenomena before toe transplantation, and also in about half of the amputated fingers without the surgery. Conversely, phantom toe phenomena occurred in 13 (17%) patients. Although some patients had mild-to-moderate unpleasant phantom sensations, none had severe or distressing phantom finger pain or phantom toe pain. It is concluded that phantom phenomena occurred in both finger and toe amputations, and that toe-to-finger transplantation appeared to facilitate the disappearance of phantom phenomena not only in the transplanted fingers but also in the amputated but untransplanted fingers. Possible mechanisms for these observations are discussed.

Adolescent↗
PubMed2003

A mode hypothesis for finger interaction during multi-finger force-production tasks.

Finger forces are known to change involuntarily during multi-finger force-production tasks, even when a finger's involvement in a task is not consciously changed (the enslaving effect). Furthermore, during maximal force-production (MVC) tests, the force produced by a given finger in a multi-finger task is smaller than the force generated by this finger in its single-finger MVC test (the force-deficit effect). A set of hypothetical control variables - modes - is introduced. Modes can be estimated based on individual finger forces during single-finger MVC tests. We show that a simple formal model based on modes with only one free parameter accounts for finger forces during a variety of multi-finger MVC tests. The free parameter accounts for the force-deficit effect, and its value depends only on the number of explicitly involved fingers. This approach offers a simple framework for the analysis of finger interaction during multi-finger actions.

Biomechanical Phenomena↗
PubMed2001

Multiconnection of identical zinc finger: implication for DNA binding affinity and unit modulation of the three zinc finger domain.

Cys(2)-His(2)-type zinc finger proteins have a tandemly repeated array structure consisting of independent finger modules. They are expected to elevate the DNA binding affinity and specificity by increasing the number of finger modules. To investigate the relation between the number and the DNA binding affinity of the zinc finger, we have designed the two- to four-finger peptides by connecting the central zinc finger (finger 2) of Sp1 with the canonical linker sequence, Thr-Gly-Glu-Lys-Pro. Gel mobility shift assays reveal that the cognate three- and four-finger peptides, Sp1(zf222) and Sp1(zf2222), strongly bind to the predicted target sequences, but the two-finger peptide, Sp1(zf22), does not. Of special interest is the fact that the dissociation constant for Sp1(zf2222) binding to the target DNA is comparable to that for Sp1(zf222). The methylation interference, DNase I and hydroxyl radical footprintings, and circular permutation analyses demonstrate that Sp1(zf2222) binds to its target site with three successive zinc fingers and the binding of the fourth zinc finger is inhibited by DNA bending induced by the binding of the three-finger domain. The present results strongly indicate that the zinc finger protein binds to DNA by the three-finger domain as one binding unit. In addition, this information provides the basis for the design of a novel multifinger protein with high affinity and specificity for long DNA sequences, such as chromosomal DNAs.

Base Sequence↗
PubMed1993

Role of TFIIIA zinc fingers in vivo: analysis of single-finger function in developing Xenopus embryos.

The Xenopus 5S RNA gene-specific transcription factor IIIA (TFIIIA) has nine consecutive Cys2His2 zinc finger motifs. Studies were conducted in vivo to determine the contribution of each of the nine zinc fingers to the activity of TFIIIA in living cells. Nine separate TFIIIA mutants were expressed in Xenopus embryos following microinjection of their respective in vitro-derived mRNAs. Each mutant contained a single histidine-to-asparagine substitution in the third zinc ligand position of an individual zinc finger. These mutations result in structural disruption of the mutated finger with little or no effect on the other fingers. The activity of mutant proteins in vivo was assessed by measuring transcriptional activation of the endogenous 5S RNA genes. Mutants containing a substitution in zinc finger 1, 2, or 3 activate 5S RNA genes at a level which is reduced relative to that in embryos injected with the message for wild-type TFIIIA. Proteins with a histidine-to-asparagine substitution in zinc finger 5 or 7 activate 5S RNA genes at a level that is roughly equivalent to that of the wild-type protein. Zinc fingers 8 and 9 appear to be critical for the normal function of TFIIIA, since mutations in these fingers result in little or no activation of the endogenous 5S RNA genes. Surprisingly, proteins with a mutation in zinc finger 4 or 6 stimulate 5S RNA transcription at a level that is significantly higher than that mediated by similar concentrations of wild-type TFIIIA. Differences in the amount of newly synthesized 5S RNA in embryos containing the various mutant forms of TFIIIA result from differences in the relative number and/or activity of transcription complexes assembled on the endogenous 5S RNA genes and, in the case of the finger 4 and finger 6 mutants, result from increased transcriptional activation of the normally inactive oocyte-type 5S RNA genes. The remarkably high activity of the finger 6 mutant can be reproduced in vitro when transcription is carried out in the presence of 5S RNA. Disruption of zinc finger 6 results in a form of TFIIIA that exhibits reduced susceptibility to feedback inhibition by 5S RNA and therefore increases the availability of the transcription factor for transcription complex formation.

Animals↗
PubMed2005

Single zinc-finger extension: enhancing transcriptional activity and specificity of three-zinc-finger proteins.

In order to demonstrate that an existing zinc-finger protein can be simply modified to enhance DNA binding and sequence discrimination in both episomal and chromatin contexts using existing zinc-finger DNA recognition code data, and without recourse to phage display and selection strategies, we have examined the consequences of a single zinc-finger extension to a synthetic three-zinc-finger VP16 fusion protein, on transcriptional activation from model target promoters harbouring the zinc-finger binding sequences. We report a nearly 10-fold enhanced transcriptional activation by the four-zinc-finger VP16 fusion protein relative to the progenitor three-finger VP16 protein in transient assays and a greater than five-fold enhancement in stable reporter-gene expression assays. A marked decrease in transcriptional activation was evident for the four-zinc-finger derivative from mutated regulatory regions compared to the progenitor protein, as a result of recognition site-size extension. This discriminatory effect was shown to be protein concentration-dependent. These observations suggest that four-zinc-finger proteins are stable functional motifs that can be a significant improvement over the progenitor three-zinc-finger protein, both in terms of specificity and the ability to target transcriptional function to promoters, and that single zinc-finger extension can therefore have a significant impact on DNA zinc-finger protein interactions. This is a simple route for modifying or enhancing the binding properties of existing synthetic zinc-finger-based transcription factors and may be particularly suited for the modification of endogenous zinc-finger transcription factors for promoter biasing applications.

Base Sequence↗
PubMed1997

Variations of the C2H2 zinc finger motif in the yeast genome and classification of yeast zinc finger proteins.

The PROSITE pattern Zinc_Finger_C2H2 was extended to permit the detection of all C2H2 zinc fingers and their parent proteins in the recently completed sequence of the yeast genome. Additionally, a new computer program was written that extracts other zinc binding motifs (non C2H2 'fingers'), overlapping with the classical zinc finger pattern, from the found set of yeast C2H2 fingers. The complete and correct detection of all fingers is a prerequisite for the classification of the yeast zinc finger proteins in functional terms. The detected 53 yeast C2H2 zinc finger proteins do not contain finger clusters with 10 or more repeats, as is frequently found in higher eukaryotes. Only three proteins contain four or more fingers in a cluster. Moreover, nearly all 27 yeast proteins with tandem arrays of two or three finger domains can be classified into nine subgroups with high sequence conservation in their finger clusters, in particular of their DNA recognition helices. These results and application of the recently elaborated finger/DNA recognition rules suggest that the yeast proteins belonging to the same subgroup may recognize identical or very similar DNA sites.

Amino Acid Sequence↗
PubMed2002

Finger systolic blood pressure indices for the diagnosis of vibration-induced white finger.

OBJECTIVES: To compare the accuracy of several finger systolic blood pressure indices (FSBPIs) for the diagnosis of cold-induced Raynaud's phenomenon in vibration-exposed worker groups with different prevalences of vibration-induced white finger (VWF). METHODS: The finger systolic blood pressure (FSBP) in a test finger at 10 degrees C as a percentage of the pressure at 30 degrees C, corrected for the change in systolic blood pressure in a reference finger [FSBPI(A)] or the arm [FSBPI(B)], was measured in 455 healthy controls and 874 workers exposed to hand-transmitted vibration (HTV). The following FSBPIs were also calculated: FSBPI(C), as the ratio between FSBP in the test finger at 10 degrees C and FSBP in the same finger at 30 degrees C; and FSBPI(D), as the ratio of FSBP to arm systolic blood pressure during finger cooling to 10 degrees C. The finding of zero systolic blood pressure, FSBP(0), in the cooled finger was taken as an objective sign of Raynaud's attack with complete closure of the digital arteries. RESULTS: On a group basis, all FSBPIs could discriminate between the controls and the HTV workers. In the vibration-exposed worker population, the FSBPIs were significantly lower in the subjects affected with VWF than in those without vasospastic symptoms. The lower normal limits of FSBPIs were derived from the results of the cold test in the controls and were found to vary from 50% to 60%. The FSBPI(A) showed the best sensitivity for the detection of cold-induced digital arterial hyper-responsiveness in both the total sample of HTV workers (sensitivity 87%) and most of the vibration-exposed groups with different prevalence of VWF (sensitivity from 79% to 100%). The results of the receiver operating characteristic analysis suggested a higher diagnostic accuracy of FSBPI(A) when compared with the global performance of the other FSBPIs. In the whole sample of HTV workers, the predictive value of a positive cold test varied from 73% [FSBPI(D)] to 89% [FSBP(0)] and that of a negative test ranged between 89% [FSBP(0)] and 97% [FSBPI(A)]. CONCLUSIONS: The findings of this investigation and clinical experience suggest that a discriminating threshold of FSBPI(A) <60% during finger cooling to 10 degrees C is an appropriate diagnostic criterion for the detection of abnormal cold response in the digital arteries of most vibration-exposed workers with a true history of symptoms of finger whiteness at the medical interview.

Adult↗
PubMed1992

Solution structures of two zinc-finger domains from SWI5 obtained using two-dimensional 1H nuclear magnetic resonance spectroscopy. A zinc-finger structure with a third strand of beta-sheet.

This paper describes the detailed three-dimensional structures of two zinc-finger domains from the yeast transcription factor SWI5, calculated using the results of the n.m.r. experiments described in the accompanying paper. The structure of finger 2 is essentially similar to those previously obtained by others for isolated, synthetic single zinc-finger domains in solution, and for the three zinc-finger peptide Zif268 in its crystalline complex with DNA. The N-terminal half of the sequence forms a two-stranded, irregular beta-sheet containing both of the metal-binding cysteine residues, while the remainder of the structure forms a helix. Approximately the first half of this helix is alpha-helical, whereas the C-terminal portion, including the two metal-binding histidine residues, is 3(10) helical. Four invariant hydrophobic residues form a core to the structure. In contrast to all previously described structures of zinc-finger domains, finger 1 has an additional strand in the beta-sheet, formed by residues N-terminal to the formal start of the finger motif. This additional strand plays a role in stabilising the folded form of finger 1, since a two-finger peptide lacking the N-terminal residues showed folded structure in finger 2 but not in finger 1.

Amino Acid Sequence↗
PubMed2003

Finger interactions studied with transcranial magnetic stimulation during multi-finger force production tasks.

OBJECTIVE: We used transcranial magnetic stimulation (TMS) to investigate interactions among neuromuscular complexes involved in force production by individual fingers of a hand during single- and multi-finger tasks. METHODS: Subjects were asked to press with the fingertips at various levels of force using different finger combinations. TMS was applied over the M1 cortical hand area during constant force production. TMS-induced increments in fingertip forces were analyzed, as well as motor evoked potentials (MEPs) in flexor digitorum superficialis. RESULTS: Both MEP size and individual force increments had inverted U-shaped dependences on the background force (peak responses were seen at about 50% of the maximal force). Similar relationships were obtained when subjects were asked to produce different forces with the same finger combination or the same total force with different finger combinations. The relationships were similar when the force was produced by explicitly instructed fingers or by other fingers of the hand. Effects of TMS on the force of a finger showed a strong dependence on the background force produced by this finger and minimal or no dependence on forces produced by other fingers of the hand. CONCLUSIONS: Overall, TMS applied over M1 revealed little interaction among fingers. This supports the notion of digit-specific compartments in multi-digit extrinsic muscles of the hand and suggests that these compartments possess a high degree of physiological independence.

Adult↗
PubMed1992

External finger forces in submaximal five-finger static pinch prehension.

Small conductive polymer force sensors were attached to the distal phalangeal pads for measuring individual finger forces exerted during submaximal static pinch. A linear force summing strain gauge dynamometer for measuring resultant five-finger pinch force was grasped vertically using a neutral wrist posture. Individual finger forces were measured at fixed total pinch force levels of 10%, 20%, and 30% of maximum voluntary exertion using pinch spans of 45 mm and 65 mm. Total pinch force and individual finger forces were also measured while similarly grasping the dynamometer and supporting fixed weights for 1.0 kg, 1.5 kg, and 2.0 kg loads using pinch spans of 45 mm and 65 mm. The index and middle fingers exerted more than 3 N greater average force than the ring and small fingers for the fixed total pinch force task. No significant individual finger force differences were observed at the 10% maximum voluntary exertion level, however both the index and middle fingers exerted more than 5 N greater force than the ring and small fingers at the 30% maximum voluntary exertion level. The average contribution of the index, middle, ring, and small fingers were 33%, 33%, 17%, and 15%, respectfully, for the fixed total pinch force task. As exertion level increased from 10% to 30%, the contribution of the middle finger was not constant increasing from 25% to 38%. Total pinch force increased from 15 N to 30 N when the load weight increased from 1.0 kg to 2.0 kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2000

Changes in cold-induced vasodilatation, pain and cold sensation in fingers caused by repeated finger cooling in a cool environment.

To examine how repeated cooling of fingers with a rest pause schedule at work affects cold-induced vasodilatation (CIVD), pain and cold sensation in fingers, six healthy men aged 21 to 23 years immersed their left index fingers six times in stirred water at 10 degrees C for 10 minutes. After each cold-water immersion of the fingers, 5-minute rest pause was taken to observe the recovery process of the indicators. This cold-water immersion/rest pause test was carried out in a range of three ambient temperature conditions: 30 degrees C (warm), 25 degrees C (thermoneutral), and 20 degrees C (cool) as experienced in daily life. At the ambient temperatures of 30 degrees C and 25 degrees C, marked CIVD response occurred and the CIVD reactivity did not significantly change upon repetition of cold-water immersion. The lowered finger skin temperature also tended to recover quickly to the pre-immersion level during each post-immersion rest period. At the ambient temperature of 20 degrees C, however, the CIVD response weakened continuously upon repetition of immersion and almost disappeared during the final immersion. The recovery of finger skin temperature during each post-immersion rest was gradually delayed upon repetition of immersion. At every ambient temperature, finger pain and cold sensation induced by each cold-water immersion significantly decreased upon repetition of immersion and completely disappeared during each post-immersion rest period. Oral temperature during the experiment showed no significant change at the ambient temperatures of 25 degrees C and 30 degrees C, but it decreased significantly at the ambient temperature of 20 degrees C. These results suggest that in a cool work environment where the body core temperature is liable to decrease, repeated finger cooling may weaken CIVD reactivity and delay the recovery of finger temperature during post-immersion rest periods. In such lower ambient temperature work conditions, subjective judgements such as the decrease in finger pain and cold sensation during repeated finger cooling and the absence of them during post-immersion rest may not be reliable indicators for monitoring the risk of progressive tissue cooling and frostbite formation.

Adult↗
PubMed1998

Characterization of multijoint finger stiffness: dependence on finger posture and force direction.

The two-dimensional static stiffness of the index finger was measured with the interphalangeal joints in flexed and extended postures. The stiffness of the relaxed finger was compared with the stiffness when voluntary force was exerted in different directions. The finger stiffness was found to be anisotropic, with the direction of greatest stiffness being approximately parallel to the proximal phalange of the finger. This direction was relatively unaffected by finger posture or direction of finger force. Finger stiffness was more anisotropic when the interphalangeal joints were extended than flexed. The stiffness was most anisotropic when the interphalangeal joints were extended and force was being exerted in the direction of pointing, while it was least anisotropic when the interphalangeal joints were flexed and force was being exerted in directions normally associated with pinching and tapping actions. The stiffness of the individual finger joints was computed and the relation between stiffness and joint torque was examined. Previous studies, which examined single finger joints in isolation, had found that joint stiffness varied in a linear fashion with net joint torque. In contrast, we did not find a monotonic relation between joint stiffness and net joint torque, which we attributed to the need to vary the amount of cocontraction of antagonistic muscles when controlling the direction of finger force.

Adult↗