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Cloning and characterization of a novel human gene encoding a zinc finger protein with 25 fingers.

This study reports cloning and characterization of a human cDNA encoding a novel human zinc finger protein, ZFD25. ZFD25 cDNA is 6118 bp long and has an open reading frame of 2352 bp that encodes a 783 amino acid protein with 25 C2H2-type zinc fingers. The ZFD25 cDNA also contains a region with high sequence similarity to the Krüppel-associated box A and B domain in the 5'-untranslated region, suggesting that ZFD25 belongs to the Krüppel-associated box zinc finger protein family. The ZFD25 gene was localized to chromosome 7q11.2. Northern blot analysis showed that ZFD25 was expressed in a wide range of human organs. In cultured endothelial cells, the mRNA level was decreased upon serum starvation.

Amino Acid Sequence↗

Identification of four CCCH zinc finger proteins in Xenopus, including a novel vertebrate protein with four zinc fingers and severely restricted expression.

Tristetraprolin (TTP), the prototype of a class of CCCH zinc finger proteins, is a phosphoprotein that is rapidly and transiently induced by growth factors and serum in fibroblasts. Recent evidence suggests that a physiological function of TTP is to inhibit tumor necrosis factor alpha secretion from macrophages by binding to and destabilizing its mRNA (Carballo, E., Lai, W.S., Blackshear, P.J., 1998. Science, 281, 1001-1005). To investigate possible functions of CCCH proteins in early development of Xenopus, we isolated four Xenopus cDNAs encoding members of this class. Based on 49% overall amino acid identity and 84% amino acid identity within the double zinc finger domain, one of the Xenopus proteins (XC3H-1) appears to be the homologue of TTP. By similar analyses, XC3H-2 and XC3H-3 are homologues of ERF-1 (cMG1, TIS11B) and ERF-2 (TIS11D). A fourth protein, XC3H-4, is a previously unidentified member of the CCCH class of vertebrate zinc finger proteins; it contains four Cx8Cx5Cx3H repeats, two of which are YKTEL Cx8Cx5Cx3H repeats that are closely related to sequences found in the other CCCH proteins. Whereas XC3H-1, XC3H-2, and XC3H-3 were widely expressed in adult tissues, XC3H-4 mRNA was not detected in any of the adult tissues studied except for the ovary. Its expression appeared to be limited to the ovary, oocyte, egg and the early embryonic stages leading up to the mid-blastula transition. Its mRNA was highly expressed in oocytes of all ages, and was enriched in the animal pole cytosol of mature oocytes. Maternal expression was also seen with the other three messages, suggesting the possibility that these proteins are involved in regulating mRNA stability in oocyte maturation and/or early embryogenesis.

Amino Acid Sequence↗

C-terminal retroviral-type zinc finger domain from the HIV-1 nucleocapsid protein is structurally similar to the N-terminal zinc finger domain.

Two-dimensional NMR spectroscopic and computational methods were employed for the structure determination of an 18-residue peptide with the amino acid sequence of the C-terminal retroviral-type (r.t.) zinc finger domain from the nucleocapsid protein (NCP) of HIV-1 [Zn(HIV1-F2)]. Unlike results obtained for the first retroviral-type zinc finger peptide, Zn(HIV1-F1), [Summers et al. (1990) Biochemistry 29, 329], broad signals indicative of conformational lability were observed in the 1H NMR spectrum of Zn-(HIV1-F2) at 25 degrees C. The NMR signals narrowed upon cooling to -2 degrees C, enabling complete 1H NMR signal assignment via standard two-dimensional (2D) NMR methods. Distance restraints obtained from qualitative analysis of 2D nuclear Overhauser effect (NOESY) data were used to generate 30 distance geometry (DG) structures with penalties (penalty = sum of the squared differences between interatomic distances defined in the restraints file and in the DG structures) in the range 0.02-0.03 A2. All structures were qualitatively consistent with the experimental NOESY spectrum based on comparisons with 2D NOESY back-calculated spectra. Superposition of the backbone atoms (C, C alpha, N) for residues C(1)-C(14) gave pairwise RMSD values in the range 0.16-0.75 A. The folding of Zn(HIV1-F2) is very similar to that observed for Zn(HIV1-F1). Small differences observed between the two finger domains are localized to residues between His(9) and Cys(14), with residues M(11)-C(14) forming a 3(10) helical corner.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Performance reduction in finger amputees when reaching and operating common control devices: a pilot experimental investigation using a simulated finger disability.

This paper reports results of an experimental laboratory investigation to determine if finger amputations (most pervasive upper extremity injury in the United States) result in significant work performance deterioration in tasks requiring operation of common control devices found in industrial settings. Ten male student volunteers from the University of Cincinnati participated in this study. The finger disability simulated was of an extreme nature, and was defined as the loss of four fingers in the preferred hand and the thumb in the nonpreferred hand. While being seated, participants activated 5 types of industrial control devices (a rotary dial, a push button, a toggle switch, a castor wheel, and a rocker switch). The controls were assembled on a device attached to a cylindrical pole, such that the control assembly could move up and down the cylindrical pole. The vertical height of control location (15, 20, and 30 in. from the seat reference point) and angle of control location in vertical plane (0 degree, 45 degrees, 90 degrees, and 135 degrees) were varied in the experiment. Participants also had their torso restrained or unrestrained while reaching and activating controls, in addition to the presence or absence of the simulated disability in each participant. Functional reaches and arm reaches from the wall were measured for participants in the sample to determine the distances at which to place the control pole assembly. If a participant was able to reach the control, the time taken to activate and operate the control was recorded. Overall results indicate that participants took significantly longer (p < 0.05) to activate controls in the presence of the simulated disability. Physical restraint did not significantly alter performance provided the participant was able to reach the control. The type of control and the height of location of the control also significantly affected work performance.

Adult↗

Conversion of the E1A Cys4 zinc finger to a nonfunctional His2,Cys2 zinc finger by a single point mutation.

Trans-activation by the adenovirus E1A 289R protein requires a zinc finger defined by Cys-154, Cys-157, Cys-171, and Cys-174. Whereas individually replacing the four cysteine residues with serines resulted in a loss of transactivation, only three of the Cys----Ser mutants (C157S, C171S, and C174S) lost the ability to bind Zn(II). X-ray absorption fine structure analysis revealed that, in the wild-type protein, Zn(II) is coordinated by four cysteine residues whereas in the C154S mutant, Zn(II) is coordinated by two histidines and two cysteines. The mutant protein probably retains, as ligands, two cysteines on the right side of the zinc finger (Cys-171 and Cys-174) and recruits two of the four histidines on the left side (His-149, His-152, His-158, and His-160), despite the presence of Cys-157. This finding may shed light on the general structural requirements of zinc fingers.

Adenoviridae↗

A novel member of the RING finger family, KRIP-1, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins.

The Krüppel-associated box A (KRAB-A) domain is an evolutionarily conserved transcriptional repressor domain present in approximately one-third of zinc finger proteins of the Cys2-His2 type. Using the yeast two-hybrid system, we report the isolation of a cDNA encoding a novel murine protein, KRAB-A interacting protein 1 (KRIP-1) that physically interacts with the KRAB-A region. KRIP-1 is a member of the RBCC subfamily of the RING finger, or Cys3HisCys4, family of zinc binding proteins whose other members are known to play important roles in differentiation, oncogenesis, and signal transduction. The KRIP-1 protein has high homology to TIF1, a putative modulator of ligand-dependent activation function of nuclear receptors. A 3.5-kb mRNA for KRIP-1 is ubiquitously expressed among all adult mouse tissues studied. When a GAL4-KRIP-1 fusion protein is expressed in COS cells with a chloramphenicol acetyltransferase reporter construct with five GAL4 binding sites, there is dose-dependent repression of transcription. Thus, KRIP-1 interacts with the KRAB-A region of C2H2 zinc finger proteins and may mediate or modulate KRAB-A transcriptional repressor activity.

Amino Acid Sequence↗

Differing roles for zinc fingers in DNA recognition: structure of a six-finger transcription factor IIIA complex.

The crystal structure of the six NH2-terminal zinc fingers of Xenopus laevis transcription factor IIIA (TFIIIA) bound with 31 bp of the 5S rRNA gene promoter has been determined at 3.1 A resolution. Individual zinc fingers are positioned differently in the major groove and across the minor groove of DNA to span the entire length of the duplex. These results show how TFIIIA can recognize several separated DNA sequences by using fewer fingers than necessary for continuous winding in the major groove.

Amino Acid Sequence↗

Cloning and characterization of a novel zinc finger transcriptional repressor. A direct role of the zinc finger motif in repression.

We have identified a novel transcriptional repressor, AEBP2, that binds to a regulatory sequence (termed AE-1) located in the proximal promoter region of the aP2 gene that encodes the adipose fatty acid-binding protein. Sequence analysis of AEBP2 cDNA revealed that it encodes a protein containing three Gli-Krüppel (Cys2-His2)-type zinc fingers. Northern blot analysis revealed two transcripts (4.5 and 3.5 kilobases) which were ubiquitously expressed in every mouse tissue examined. In co-transfection assays, AEBP2 repressed transcription from the homologous aP2 promoter containing multiple copies of the AE-1 sequence. Moreover, a chimeric construct encoding a fusion AEBP2 protein with the Gal4 DNA-binding domain was able to repress the transcriptional activity of a heterologous promoter containing the Gal4-binding sequence. The transcriptional repression function of AEBP2 was completely abolished when one of the conserved histidine residues and a flanking serine residue in the middle zinc finger were replaced with an arginine residue. The defective transcriptional repression function of the mutant derivative was due neither to lack of expression nor to a failure to localize to the nucleus. Moreover, both the wild-type and mutant derivative of either the histidine-tagged recombinant AEBP2 proteins or the in vitro translated Gal4-AEBP2 fusion proteins were equally able to bind to the target DNA. These results suggest that a portion of the zinc finger structure may play a direct role in transcriptional repression function, but not in DNA binding.

Amino Acid Sequence↗

Hand orthosis for various finger impairments--the K U finger splint.

The K U (Kumamoto University) finger splint has been manufactured for the purpose of developing an effective hand orthosis for various finger impairments using simple parts and materials. By combining the W type orthosis for which piano wire is mostly used, and the S type for which fishing line is mainly used, it has been used to good effect on patients with several kinds of finger impairments. The fabrication and adjustment of the orthosis is simple and if the material is in kit form, a doctor or an occupational therapist can at once construct one and give it to a patient. For this reason, the patient will not lose the chance of timely treatment.

Fingers↗

Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Krüppel-like factor, a novel zinc finger repressor.

The expression of CLC-K1 and CLC-K2, two kidney-specific CLC chloride channels, is transcriptionally regulated on a tissue-specific basis. Previous studies have shown that a GA element near their transcriptional start sites is important for basal and cell-specific activities of the CLC-K1 and CLC-K2 gene promoters. To identify the GA-binding proteins, the human kidney cDNA library was screened by a yeast one-hybrid system. A novel member of the Cys2-His2 zinc finger gene designated KKLF (for "kidney-enriched Krüppel-like factor") and the previously isolated MAZ (for "myc-associated zinc finger protein") were cloned. KKLF was found to be abundantly expressed in the liver, kidneys, heart, and skeletal muscle, and immunohistochemistry revealed the nuclear localization of KKLF protein in interstitial cells in heart and skeletal muscle, stellate cells, and fibroblasts in the liver. In the kidneys, KKLF protein was localized in interstitial cells, mesangial cells, and nephron segments, where CLC-K1 and CLC-K2 were not expressed. A gel mobility shift assay revealed sequence-specific binding of recombinant KKLF and MAZ proteins to the CLC-K1 GA element, and the fine-mutation assay clarified that the consensus sequence for the KKLF binding site was GGGGNGGNG. In a transient-transfection experiment, MAZ had a strong activating effect on transcription of the CLC-K1-luciferase reporter gene. On the other hand, KKLF coexpression with MAZ appeared to block the activating effect of MAZ. These results suggest that a novel set of zinc finger proteins may help regulate the strict tissue- and nephron segment-specific expression of the CLC-K1 and CLC-K2 channel genes through their GA cis element.

Amino Acid Sequence↗

Simultaneous dorsal dislocation of the interphalangeal joints in ring finger with proximal interphalangeal joint dislocation of the middle finger: case report and review of the literature.

A 30-year-old amateur goalkeeper sustained simultaneous dislocation of the proximal and distal interphalangeal joints of the ring finger and of the proximal interphalangeal joint of the middle finger following a hyperextension injury. This was reduced under a local anaesthetic. Neighbour finger strapping and early mobilisation achieved an excellent functional outcome when reviewed at eight weeks after the initial injury.

Adult↗

Hypohydration effect on finger skin temperature and blood flow during cold-water finger immersion.

This study was conducted to determine whether hypohydration (Hy) alters blood flow, skin temperature, or cold-induced vasodilation (CIVD) during peripheral cooling. Fourteen subjects sat in a thermoneutral environment (27 degrees C) during 15-min warm-water (42 degrees C) and 30-min cold-water (4 degrees C) finger immersion (FI) while euhydrated (Eu) and, again, during Hy. Hy (-4% body weight) was induced before FI by exercise-heat exposure (38 degrees C, 30% relative humidity) with no fluid replacement, whereas during Eu, fluid intake maintained body weight. Finger pad blood flow [as measured by laser-Doppler flux (LDF)] and nail bed (T(nb)), pad (T(pad)), and core (T(c)) temperatures were measured. LDF decreased similarly during Eu and Hy (32 +/- 10 and 33 +/- 13% of peak during warm-water immersion). Mean T(nb) and T(pad) were similar between Eu (7.1 +/- 1.0 and 11.5 +/- 1.6 degrees C) and Hy (7.4 +/- 1.3 and 12.6 +/- 2.1 degrees C). CIVD parameters (e.g., nadir, onset time, apex) were similar between trials, except T(pad) nadir was higher during Hy (10.4 +/- 3.8 degrees C) than during Eu (7.9 +/- 1.6 degrees C), which was attributed to higher T(c) in six subjects during Hy (37.5 +/- 0.2 degrees C), compared with during Eu (37.1 +/- 0.1 degrees C). The results of this study provide no evidence that Hy alters finger blood flow, skin temperature, or CIVD during peripheral cooling.

Adult↗

Pathological changes observed in the finger biopsy of patients with vibration-induced white finger.

Lesion biopsies of 60 fingers from 30 patients with vibration-induced white finger (VWF) and control observations from seven fingers of five referents demonstrated three main characteristic pathological changes. First, in each case, the muscular layers of the arteries revealed intense thickening with strong hypertrophy of individual muscle cells without intimal fibrosis. Periarterial fibrosis was also noted. Arteriosclerosis with foamy cells, lipid deposition, and fibrous sclerosis was occasionally observed. The second main change was demyelinating neuropathy in the peripheral nerves in which a marked loss of nerve fibers had occurred. There was also an increase in the number of Schwann cells and fibroblasts with strong collagen formation. Severe loss of myelin sheath frequently occurred, and relatively smaller axons without myelin which appeared to have regenerated were observed. Perineural fibrosis was also noted. In the third main pathological change connective tissues with collagen were increased not only in the perivascular and perineural lesions, but also abundantly in the corium of the skin. The elastic fibers there had been destroyed. These three principal pathological changes are very useful for the histopathological diagnosis of VWF.

Adult↗

[Index finger pollicization for congenitally deficient first finger of the hand in children].

Pollicization is a single-stage neurovascular pedicle transfer of the index digit to function as a thumb. The objective of this study is to investigate the results of index finger pollicization for correction of congenital deficiency of the first ray in pediatric hand. We have done 6 pollicizations of index fingers in 6 hands (there were 2 right hands, 2 left hands, and 1 bilaterally) in 5 patients (4 boys and 1 girl) who had absent or nonfunctioning thumbs (type III-V of Blauth's classification). Associated anomalies where numerous and included radial club hand, mirror hand and cardiovascular and urologic anomalies. The average time of Kirschner wire extraction was 32 days (30 to 36 days) and to beginning the hand rehabilitation at 5 degrees to 10 degrees day. The average age at pollicization was 5.5 years (range 2 to 8 years), and follow-up averaged 8 years (5 to 11 years). The cosmetic and functional results were excellent, with manual dexterity of prehension and opposition. Pollicization in children can be performed at least 2 years of age, to due of minor risk of neurovascular lesion but without delayed the cortical representation of the pollicized finger.

Child↗

An isolated ring finger metacarpal shaft fracture?--beware an associated little finger carpometacarpal joint dislocation.

Dislocations of the ulnar carpometacarpal joint are easily missed because of a low index of suspicion as well as their subtle clinical and radiological features. Often, the presence of a more obvious adjacent injury also draws attention away from the carpometacarpal joint. Two cases of ring finger metacarpal shaft fractures with associated little finger carpometacarpal joint dislocations are presented. In both cases, the metacarpal fractures were diagnosed but the carpometacarpal joint dislocations were initially overlooked. The presence of an apparently isolated ring finger metacarpal fracture due to an indirect force should raise the possibility of an associated carpometacarpal joint injury.

Adult↗

Dual-Finger Preferred-Speed Tapping: Effects of Coordination Mode and Anatomical Finger and Limb Pairings.

Interlimb and interfinger coordination were examined in a dual-finger tapping paradigm in which 16 subjects performed at preferred frequencies. Three bimanual finger combinations, in random order (2 index; 2 middle; and 1 index and 1 middle), were performed in in-phase and antiphase coordination modes, in addition to 1 unimanual combination (antiphase index-middle). Relative phase means were within 3&percent; accuracy for all conditions. A lower tapping frequency was found in all antiphase vs. in-phase conditions, accompanied by lower phasing variability and lower intrafinger consistency in the antiphase. When frequency was changed from the preferred rate, the 2 coordination modes became more alike in variability and, within the same frequency range, demonstrated no significant differences. The bimanual mixed-fingers tapping tended to have significantly lower phasing values (a small fixed point drift) and higher tapping frequencies than the symmetric conditions. The unimanual task was similar to all other antiphase conditions. Changes in preferred frequency with different coordination modes may be related to differing perceptual informational constraints. Current models addressing natural frequencies of coupled oscillators do not account for the present data.

Journal Article↗

The medical and surgical treatment of finger clubbing and hypertrophic osteoarthropathy. A blind study with colchicine and a surgical approach to finger clubbing reduction.

In fourteen patients affected with pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy, the efficacy of colchicine (0.5 mg day for one month) versus placebo on the main clinical features of the disease (finger clubbing, arthritis and pachydermia) was evaluated. In addition, in one patient the usefulness of surgical reduction of clubbed fingertips was investigated. Colchicine did not demonstrate any appreciable effect on finger clubbing (expressed in degrees) or pachydermia, while an effect on arthralgia (as evaluated by the Ritchie Index and Pain Scale) was observed. The surgical treatment of clubbed fingertips failed to show a satisfactory and stable reduction of the fingertips; two months after surgery the nail matrix apparently produced new tissue, once again enlarging and deforming the finger. These results suggest that low dose colchicine cannot be considered the drug of first choice for the treatment of PDP, while higher dosages, although effective, are not tolerated because of the severe side effects. An effective medical and surgical treatment for PDP will be found only when the pathogenetic mechanisms of the disease are clarified.

Adult↗

Finger ridge count and finger print pattern in maturity onset diabetes mellitus.

Total finger ridge count, absolute finger ridge count and finger print pattern were studied in 150 maturity onset diabetes mellitus patients and compared to 120 controls. Significant findings were: in males, with both hands combined and separately (i) an increase in radial and ulnar loops and arches (ii) A decrease in whorls. (iii) In females, an increase in ulnar loops and a decrease in whorls in the left hand was observed.

Dermatoglyphics↗