XG100.00%

XG

Influence of xanthan gum (XG) on the properties of the solution containing 3.0 wt% sodium caseinate (CN) was estimated firstly by zeta potential, hydrodynamic diameter (DH) and interfacial tension. CN–XG mixture solutions showed larger DH and lower negative zeta potential at higher XG concentration, indicating that molecule interactions may take place in solution. The surface activity of CN was improved with addition of XG at 0.01 wt%, while it weakened to a great extent at 0.04 wt% XG. Then, the influence of XG on the concentrated (36 wt%) emulsion, stabilized with 3.0 wt% CN was assessed by droplet diameter and dispersion characteristics, apparent viscosity, surface protein concentration and microstructure. Results showed that emulsion without XG, characterized by the lowest surface protein concentration and apparent viscosity, showed no sign of flocculation but coarse oil droplets. Increase in XG concentration led to an increase followed by a decrease in d4,3, uniformity values and partial coalescence of fat, while inversely, surface protein concentration decreased firstly and then increased. CLSM images showed extensive enrichment region of XG and depletion flocculation at XG concentration above 0.01 wt%.

Graphical abstract

Confocal micrographs of whipping cream (36 wt% anhydrous milk fat, 3 wt% CN, and pH 6.8) with selected XG concentrations. Scale bar represents 50 μm. Particle size distribution of emulsions determined by light scattering (Mastersizer 2000) is superimposed on the micrographs, with horizontal scale numbers indicate particle size (μm) and vertical scale numbers indicate volume (%).

Wear

Volume 302, Issues 1–2, April–May 2013, Pages 854-862

Effects of the sub-zero treatment condition on microstructure, mechanical behavior and wear resistance of W9Mo3Cr4V high speed steel

Author links open overlay panelX.G.YanabD.Y.Lib

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X-linked agammaglobulinemia (XLA) patients manifest a very low production of immunoglobulins (Ig) of all classes and plasma cells are virtually absent. The XLA gene plays a crucial role in the transition of pre-B cells to later B cell stages, as hardly any slg-positive B lymphocytes can be detected. In the bone marrow almost normal numbers of pre-B lymphocytes are present. These cytoplasmatic Cμ+ pre-B lymphocytes appear to express truncated M heavy chain molecules lacking the variable region segment. The T lymphocyte compartment is intact: the numbers of mature T cell receptor (TcR) αβ expressing T lymphocyte populations and their proliferative responses to antigens are normal. That the B cells are primary and exclusively affected was proven by X-chromosome inactivation studies. There is no evidence that the XLA gene is directly involved in the Ig gene rearrangements since B lymphoblastoid cell lines (BLCLs) established from peripheral blood of XLA patients were found to produce IgM molecules composed of complete Ig heavy and light chains and were shown to contain normal VHDJH recombinations. The data do not exclude the involvement of the XLA gene in a B cell specific process that makes the Ig loci accessible for recombination. Investigations on the degree of diversity of immunoglobulins generated by XLA patients exposed no limitations in the VH family usage. Sequence analysis of expressed VH3 and VH4 rearrangements however revealed that some genetic elements of the Ig locus might be overrepresented and that a high portion of rearrangements was generated by unconventional mechanisms. By restriction length polymorphism (RFLP) and pulsed field gel electrophoreses analyses the XLA gene was mapped to an 8- to 12-Mb DNA fragment located in the Xq22 region. The known location of the XLA gene on the X-chromosome with closely linked RFLP markers and the availability of X-chromosome inactivation assays provides methods for carrier detection and prenatal diagnosis.

Blood Group Xg System

Related terms:

X Chromosome

Dosage Compensation

X-Inactivation

Nested Gene

Cell Culture

Sex Chromosome

Autosomal Dominant Inheritance

Placental Mammal

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B-Cell Defects: From X-linked Recessive to Autosomal Recessive Agammaglobulinemia

Jerry A. Winkelstein, C.I. Edvard Smith, in Primary Immunodeficiency Disorders, 2014

Identification of the molecular genetic defect

In the early 1960s, it was reported that the XLA gene was not linked to the Xg blood group determinants (27), but it was not until the mid-1980s that its location was revealed with high resolution. Thus, the XLA gene was first mapped to the Xq21.3-Xq22 region of the long arm (28, 29) and, later, with the aid of new markers (30, 31), its position was determined with greater precision. However, while the final aim of the mapping studies was the identification of the mutated gene, as it often turned out, it was not the XLA gene mappers who succeeded in cloning of disease gene, and the corresponding protein remained elusive. At least two papers suggested the possibility of an enzyme defect prior to the cloning, but these proposals were simply hypotheses (32, 33).

Instead, in 1991–1992, two groups independently initiated work which subsequently would result in the identification of the disease gene. In Europe, a collaborative effort between researchers in the UK and Sweden first resulted in the identification of an unrecombined yeast artificial chromosome (YAC) y178-3 from the implicated region on the X chromosome. Subsequently, the y178-3 clone was used to enrich cDNAs from B-lineage cells. The enriched cDNAs thereafter served as probes in Southern blots made from restriction enzyme-digested genomic DNA obtained from a number of XLA patients in order to identify alterations suggestive of a mutation. The implicated mutations in a novel gene were verified by sequencing, and "Patient A", the first patient with an identified mutation, was a child originating from Southern Sweden (9). Simultaneously at UCLA in the USA, in an effort to identify new tyrosine kinases in B-cell progenitors, an unknown transcript was identified and the corresponding gene found to locate on the X chromosome. Because of the many forms of X-linked recessive human disorders, which almost exclusively affect males, this immediately made the corresponding gene a candidate for a human disease. While the exact mutations were not pinpointed in this report, reduction in, or the absence of mRNA, protein expression, and kinase activity were observed in XLA pre-B- and B-cell lines (10). The two papers complemented each other and received major attention far outside the immunodeficiency arena, owing to the fact that this was one of the first examples of a tyrosine kinase implicated in human inherited disease. The cloning of the BTK gene took place during an exciting era when it was still possible to identify new genes by linkage analysis and positional cloning. According to Francis S. Collins, director of the Human Genome Project, BTK became the 17th gene identified by positional cloning (23). In the immunodeficiency field, it was preceded only by the CYBB gene (causing chronic granulomatous disease), which was detected through a combination of linkage analysis and large gene deletions on the short arm of the X chromosome (34).

When the corresponding papers were in press, one of us, Edvard Smith from the European team, learned that the same gene might also have been cloned in the USA. The first investigator he contacted was not involved, but mentioned Owen N. Witte as a likely candidate. Owen N. Witte was reached by phone, and it was realized that both teams presumably had identified the very same gene. After the phone call, in this pre-Internet era, the manuscripts were simultaneously faxed between UCLA and Karolinska Institutet, and the identity of the gene was conclusively verified. The European group had named the gene ATK (agammaglobulinemia tyrosine kinase), whereas the UCLA team called it BPK (B-cell progenitor kinase). When the phone call was made it was already too late to adopt a common name to be used in the cloning articles, but a novel name was agreed on only a month later, when the defect in Xid mice was found to originate from a missense mutation in the corresponding mouse gene (35, 36). The new name BTK, Bruton tyrosine kinase, makes use of two letters from both the original abbreviations and, in this way, the unnecessary use of two parallel names was avoided. BTK also became the official gene name. The gene product is involved in transducing signals from the cell membrane, with the B-cell receptor (BCR) and the pre-BCR as major origins of such signaling.

Immediately prior to the first public oral report of the gene discovery, which would take place at the B-cell Keystone Meeting in Taos, New Mexico in the beginning of 1993, Smith visited Boston and met with Fred Rosen, one of the pioneers in the immunodeficiency field. When asked about Dr Bruton's current whereabouts, Fred Rosen mentioned that he might still be living close to Bethesda. Coincidentally, the trip to the Keystone conference had one more scheduled stop, namely NIH, Bethesda, for a meeting with Jeffrey D. Thomas and William E. Paul on the collaborative Xid gene analysis (35). Upon arrival in Bethesda, Smith, with great curiosity, checked the hotel phonebooks and eventually found "Ogden C. Bruton, MD", with an address in Silver Spring, Maryland, located just east of Bethesda. Two days later, more than 40 years after the original patient description appeared in print, together with Jeffrey Thomas, he met with Dr Bruton and his wife Kathryn, who were already a couple at the time of the seminal 1952 paper. Interestingly, Kathryn Bruton mentioned the importance of the fact that her husband went ahead and published his early observations as a single author. She was of the opinion that if Bruton had waited, she was certain that his contribution to the discovery would have gone essentially unnoticed, and that scholars in Boston with a stronger academic standing would have received the credit. A photograph of the participants documented this meeting (Fig. 11.4) (37). It was during the NIH visit in the early 1993 that the name change to BTK was agreed upon.

Figure 11.4. One of the discoverers of the genetic defect meets the discoverer of the disease in 1993. Dr Bruton is seated, his wife Kathryn D Bruton is standing to his left, Dr Jeffrey D Thomas is standing to his right and Dr CI Edvard Smith is standing behind him.

(Reproduced with permission from (37).)

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Phenotypic Correlations of X-Chromosome Loss

E. Kirk Neely, Ron G. Rosenfeld, in Molecular Genetics of Sex Determination, 1994

A Parental Origin of the X Chromosome

Assignment of parental origin of the remaining X chromosome has been undertaken for several reasons, not only to look for clues to the etiology of X monosomy, but also to evaluate the possibility that parental origin might explain the vast phenotypic variation associated with the 45, X karyotype. The recent discovery of genomic imprinting has highlighted the theoretical basis by which parental origin could lead to the phenotypic diversity seen in Turner syndrome. Through assessment of Xg blood groups, Sanger et al. (1971) initially determined that loss of the paternal X occurred in 77% of cases. With the availability of X-chromosomal DNA probes, restriction fragment length polymorphism (RFLP) analysis was applied to this task first by Hassold et al. (1985) and subsequently by several other groups. The results have verified the finding of Sanger et al. (1971) that the X in 45, X monosomy is maternal (Xm) approximately 80% of the time, although the ratio of Xm to Xp in mosaicism and i(Xq) karyotypes may be closer to parity.

Although this information has not markedly altered notions regarding the developmental error involved in monosomy X, it has allowed for partial clarification of the phenotypic effects of parental origin of the X. The combined data from Hassold et al. (1988) and Jacobs et al. (1990), reveal no shift in the prevalence in fetal demise of either a maternally or a paternally imprinted X. Parental origin of the X therefore seems an unlikely factor in this most striking phenotypic determination. Furthermore, two studies performed to date have failed to discern other clinical differences in 45, X subjects on the basis of parental origin of the X chromosome. Although the data of Mathur et al. (1991) suggested an absence of renal abnormalities with Xp, and Lorda-Sanchez et al. (1992) reported no cardiac anomalies with Xp, the studies combined revealed no distinctions between Xm and Xp groups. Larger compilations of Xp phenotypes will be required for a definitive answer regarding differences in clinical phenotypes. Analysis of all determinations of parental origin suggests that the reduced maternal age in 45, X cases is confined to mothers of Xp individuals (Lorda-Sanchez et al., 1992).

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Ehlers–Danlos Syndrome

Peter H. Byers, in Emery and Rimoin's Principles and Practice of Medical Genetics, 2013

154.10 Other Forms of Ehlers–Danlos Syndrome

154.10.1 X-linked Ehlers–Danlos Syndrome (EDS Type V)

Beighton (1,3) described a family in which affected males had skin hyperextensibility similar to that seen in EDS type II. Joint mobility and cutaneous bruising were thought to be less extensive, but intramuscular hemorrhage was more common. There was no evidence of abnormalities in lysyl oxidase function or in collagen cross-link formation (169), as have been found in cells cultured from individuals with occipital horn syndrome (170). Linkage to the Xg blood group and color blindness were excluded in the family (171). It is unclear whether this family, instead, has an autosomal dominant form of EDS, probably a variety of the classical form, with variable expression. Until additional linkage studies can demonstrate an X-chromosomal location for this disorder, the uniqueness of the condition remains uncertain.

154.10.2 Periodontal Form of Ehlers–Danlos Syndrome (EDS Type VIII)

The periodontal form of EDS was first proposed as a separate entity on the basis of two families in which periodontal disease was accompanied by marked bruising, joint hypermobility, and skin hyperextensibility (172). The condition was inherited in an autosomal dominant fashion. In those families, affected individuals had lost most of their teeth by their early twenties as a result of gingival recession that did not appear to be primarily inflammatory. A small number of additional families have been described (97,137,173–177). Pretibial bruising is often more pronounced than expected with other forms of EDS.

Biochemical studies have failed to identify abnormalities in type I or III procollagen (174,175). The condition should be distinguished from EDS type IV, in which periodontal disease is common. The treatment of the noninflammatory gingival recession is not clear but assiduous attention to dental hygiene may be helpful. Orthodontic manipulation may lead to early loss of teeth (97). Gene mapping studies now suggest that EDS type VIII, the periodontal type, may be genetically heterogenous. One locus was mapped to a 4.5Mb region on the short arm of chromosome 12, but analysis of several candidate genes in the region was not fruitful. One the basis of those studies, there appears to be at least one additional locus and perhaps more.

154.10.3 Fibronectin Defect Form of Ehlers–Danlos Syndrome (EDS Type X)

This disorder was described in a single family, in which mild features compatible with EDS type II or III were associated with a variable disorder of platelet aggregation that could be corrected with heterologous plasma or purified fibronectin (64). Skin from one affected individual had alterations in fibril morphology. No biochemical defect in fibronectin has yet been identified. In as much as platelet aggregation defects may be a concomitant finding in some individuals with different forms of EDS (178), it is unclear that this condition warrants a unique identity.

154.10.4 Progeroid Type of Ehlers–Danlos Syndrome

Several children have now been described with progeroid facies, multiple nevi, mild mental retardation, skin hyperextensibility, bruisability, moderate skin fragility, and joint hypermobility principally in digits, with radio-ulnar synostosis and developmental delay (179,180). There is moderate variation in the clinical presentation. Inheritance is autosomal recessive and mutations have been identified in the B4GALT7 gene that encodes galactosyltransferase-I (179,181,182). The enzyme is responsible for the transfer of galactose to the xylose residue on serines in the formation of heparin sulfate and chondroitin sulfate.

154.10.5 Ehlers–Danlos Syndrome with Periventricular Heterotopia

Two reports from 2005 describe an X-linked dominant disorder, with probably male lethality, characterized by joint hypermobility, skin extensibility but without significant scarring, presentation with seizures, and the radiological finding of brain heterotopia, often in the periventricular region (7,183). Some of the individuals had arterial aneurysms, including aortic enlargement. Two similar patients had been reported previously (184,185). Surprisingly, the mutations in the families were found in the FLNA gene that encodes the protein filamin A, a protein that cross-links the actin fiber cytoplasmic network in cells. Mutations in the gene are known to cause otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia, and Melnick–Needles syndrome. The clinical differences are no doubt related to specific mutations in the gene.

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Abnormalities of Pigmentation

Richard A. Spritz, Vincent J. Hearing, in Emery and Rimoin's Principles and Practice of Medical Genetics, 2013

145.3.2.2 X-Linked Recessive Ocular Albinism

X-linked recessive ocular albinism (OA1; Nettleship–Falls ocular albinism; OMIM 300500; Table 145-1) is an X-linked recessive disorder in which affected males manifest many of the ocular features of albinism, but in which skin and hair pigmentation is generally normal (398,399). The irides are blue to brown, and optic changes of albinism include nystagmus, reduced retinal pigment with foveal hypoplasia, altered crossing of the optic nerves at the chiasm, and variable iris transillumination (268,400–405). In African-American and Japanese males, iris color is often brown and there is little iris translucency (268,405). In EUR patients, the skin typically appears normally pigmented, whereas in African-American patients with darker skin there may be scattered hypopigmented macules; these are rarely seen in the skin of EUR individuals. The melanocytes in the skin, hair follicles, and RPE are normal in size, shape, and number, but melanocytes in the skin, hair follicles, iris and retina contain giant melanosomes (called macromelanosomes), along with some normal melanosomes (268,403,406). The systemic nature of the melanosome defect in OA1 suggests that this is really a type of OCA in which the major manifestations are in the eye.

Heterozygous females exhibit ocular pigmentation changes that result from X-inactivation (401,407–410). A variegated or spotty pattern of retinal pigmentation (sometimes described as a mud-splattered mosaic pattern), which progressively becomes more coarse, and punctate areas of iris translucency are seen in 80–90% of obligate heterozygous females (401,410). Macromelanosomes are seen in the melanocytes of obligate heterozygous females. A few heterozygous females have more evident ocular changes of albinism, including nystagmus and reduced visual acuity, and these are thought to be the result of non-random X-inactivation (411).

The gene for OA1 was initially localized to the short arm of the X chromosome in linkage with the Xg blood group, and was subsequently localized to Xp22.32 (412,413) and then more precisely to Xp22.3–Xp22.2, between the markers DXS237 and DXS143 (414). The OA1 gene was subsequently identified as GPR143 (415,416), encoding G protein-coupled receptor 143. The coding sequence consists of nine exons and encodes a 404 amino acid protein that has several possible transmembrane domains, possibly with multiple isoforms (417). The mouse Gpr143 gene encodes a protein with a high degree of similarity to the human protein, including the presence of isoforms (418).

OA1 mutations consist of missense, frameshift, and splicing mutations, as well as a number of different deletions involving all or part of the GPR143 locus (419–428). Many of these deletions involve exon 2, most likely caused by unequal crossing-over between flanking Alu repeats (two Alu repeats in intron 1 and one Alu repeat in intron 2) (426,429). Other exons are also involved in deletions (419,427), and the frequency of large intragenic deletions is higher in Northern American than in European cases that have been studied (419). The missense mutations are located throughout the central coding region with some clustering between the first and second transmembrane regions in exons 1, 2, and 3. Some individuals with missense mutations also have other features, including X-linked ichthyosis and developmental delay (427).

The GPR143 protein is thought to be associated with the melanosome membrane in the melanocyte (417). GPR143 is a G protein-coupled receptor, representing a novel member of the GPCR superfamily, and has specific interactions with heterotrimeric G proteins (430). OA1 may therefore be caused by a defect in an intracellular signal transduction system. The gene is expressed at high levels in the retinal pigment epithelium and at lower levels in the brain and adrenal glands. Part of the pathogenesis of OA1 is the formation of giant macromelanosomes in melanocytes. Analysis of Gpr143-knockout mice suggests that the macromelanosomes are produced by the abnormal growth of individual melanosomes, instead of fusion of several smaller melanosomes (431). The GPR143 protein may be involved in sorting or trafficking the vesicles to developing melanosomes (432,433), with a role in reorganization of the late endosomal compartment, including enlargement of the late endosomes and a redistribution of the mannose 6-phosphate receptors as important steps in melanosome biogenesis (433). GPR143 may function as a stop signal for melanosome growth, its absence resulting in macromelanosome formation. In some respects, OA1 may thus be considered a defect of melanosome biogenesis/maturation (see below).

One large Afrikaner family has been reported with X-linked OA co-segregating with late-onset sensorineural deafness (434). Macromelanosomes were demonstrated in skin from affected males and obligate heterozygous females, and the clinical features were consistent with OA1. The locus for this condition maps to chromosome Xp22.3, suggesting overlap with OA1 (434,435), and it is unclear whether this OA-deafness phenotype is part of the OA1 spectrum or is related to a contiguous gene defect in this family. A family that contained three generations of males and females affected with congenital deafness and OA has been described, but little information on this family is available (436).

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XX Sex Reversal in the Human

Stephen S. Wachtel, in Molecular Genetics of Sex Determination, 1994

V Molecular Genetics of XX Sex Reversal

A Y-DIMA in XX Males

As noted above, Evans et al. (1979) found a 3.5 kb Y-fragment in an XX male with cytogenetic evidence of X–Y interchange. A molecular demonstration of occult Y-material in XX males was provided by Guellaen et al. (1984). The latter study involved four sporadic cases with no evidence of mosaicism. Samples of DNA were digested with restriction enzymes, fractionated, and hybridized in Southern blots with 10 single-copy Y-specific DNA probes including 47c and 50f2. The samples from cases 1 and 4 reacted with six and five of the probes, respectively, whereas DNA from case 3 reacted with a single probe. Hybridization did not occur in case 2.

The same subset of probes was reactive in each of the Y-positive cases, signaling occurrence of overlapping chromosomal segments. The authors noted that if a single piece of the Y chromosome were present in each case, the method could be used to align Y-specific DNA fragments in a deletion map. They noted that X–Y interchange could account for presence of Y-DNA in the apparent absence of the Y chromosome, especially in patient 3, in whom aberrant inheritance of the Xg blood group had been observed.

B Deletion Mapping of the Y Chromosome

Inasmuch as these data were consistent with X–Y interchange, and with occurrence of Y-fragments of differing sizes in the genomes of XX males, it now seemed feasible to map the Y chromosome by using panels of Y-specific restriction fragments. In the period following the report of Guellaen et al. (1984), a number of mapping studies were therefore undertaken (Page et al., 1985; Affara et al., 1986, 1987; Müller et al., 1986; Müller, 1987; also see Chapter 10 this volume). In the study by Vergnaud et al. (1986), 23 Y-specific probes were used to screen DNA from 19 XX males, 2 XX true hermaphrodites, and 6 patients with various structural abnormalities of the Y chromosome. The results indicated that the patients carried a single contiguous segment of the Y; this enabled construction of a map containing seven intervals, with assignment of TDF to an interval in the short arm. Y-DNA was detected in 12 of the 19 XX males tested; the amount of Y-DNA was variable among the different subjects.

By the same method, Page et al. (1987) constructed a deletion map of Yp containing 13 intervals. In one of the intervals ("1A2"), they found a probe, pDP1007, that could be used to identify Y-specific DNA in every mammal tested. The amino acid sequence corresponding to pDP1007 resembled that of regulatory proteins. In light of these findings, and because 1A2 was present in the genome of an XX male who carried only 300 kb of Y-DNA, it was proposed that the 1A2 interval included TDF (see discussions of ZFY in Chapter 1 and 2, this volume).

A comprehensive deletion map of the human Y chromosome has now been published (Vollrath et al., 1992). Based on a study of 96 patients with partial Y chromosomes (including 23 XX males), the map contains 132 loci, and 43 ordered intervals. Each interval is defined by chromosomal breakpoints and contains less than 800 kb DNA.

C X–Y Interchange in XX males: Y(+) and Y(−) Classes

As noted above, Guellaen et al. (1984) obtained early molecular evidence for X–Y interchange in XX sex reversal. More recently, by in situ hybridization with probe pDP105, which identifies sequences concentrated in Yp, Andersson et al. (1986) detected Yp-DNA in the distal short arm of one of the X chromosomes in each of three other XX males. These findings were extended in the study by Petit et al. (1987), who evaluated Y-DNA in nine XX males (eight sporadic and one brother of an XX true hermaphrodite) including two of the patients of Andersson et al. (1986).

By use of Yp probes 47z and 50f2 (Vergnaud et al., 1986), six of the nine XX males were found to be positive for Y-DNA and three, including the familial case, to be negative. Paternal Y-linked alleles were present in the six Y(+) cases (a telomeric sequence and at least one proximal locus—DXYS17 or MIC2—in five, and a telomeric sequence in one). On the other hand, the paternal X-pseudoautosomal alleles were deleted in each. This was the first demonstration by use of molecular methods that sex reversal in Y(+) XX males is correlated not only with gain of sequences in Yp, but also with loss of terminal Xp. By contrast, the entire paternal X-pseudoautosomal region was present in two of the Y(−) XX males. It is worth emphasizing that hypospadias was observed in one of the Y(−) XX males, and that the other was the brother of an XX true hermaphrodite, raising the question whether ambiguous genitalia in such cases might be related to the absence of Y-DNA.

D Ambiguous XX Males Are Y(−)

Occurrence of alternative classes of the XX male syndrome, one Y(+) and one Y(−), was confirmed by Ferguson-Smith et al. (1990a). They described 10 Y(+) XX males and four Y(−) XX males, among whom the latter were notable for gynecomastia and abnormality of the external genitalia. Male sex determination of the Y(−) XX males was attributed to mutation of an X-linked testis-determining gene. In a later report, Ferguson-Smith et al. (1990b) noted absence of the SRY gene in five Y(−) XX males and pointed out that SRY itself is not essential for male sex determination. Another SRF-negative case was described by van der Auwera et al. (1992) among six XX males evaluated by in situ hybridization [in the five Y(+) cases, SRY was found translocated to terminal Xp]. The Y(−) patient was remarkable for gynecomastia, cryptorchid testes, and small phallus (also see Abbas et al., 1990).

By the polymerase chain reaction (PCR), and by Southern blotting with 17 different Y probes, Numabe et al. (1992) analyzed loci including SRY, ZFY, and PABY in DNA from 14 XX males. Various Y sequences were identified in 8 of the XX males; none was detected in 6. Among the 6 Y(—) males, 5 exhibited hypospadias. This was not observed in any of the (Y +) XX males.

E Most XX True Hermaphrodites Are Y(−)

Using a panel of six Y-specific probes, including 47z (DXYS5), 50f2, Fr 80–11, Fr 35–11, and the Yq-specific repeats pJA1143 (DYZ1) and pHY2.1 (DYZ2), Waibel et al. (1987) studied DNA from 11 XX males and 7 XX true hermaphrodites. DNA from each of the XX males was positive for at least one of the probes in Southern blots. Although hybridization did not occur with DNA from any of the XX true hermaphrodites in these trials, one of the cases was later found to be Y(+) when probed for sequences adjacent to the pseudoautosomal boundary (Jäger et al., 1990).

In a study of XX true hermaphroditism among southern African blacks, Ramsay et al. (1988) tested DNA in 10 sporadic cases with 6 Y-specific probes (pDP132, pDP61, pDP105, pDP31, pDP97, and pY431-HinfA). Hybridization was not observed in any case. Later, those authors tested pDP1007 (ZFY) in TaqI digests from several of these and other cases. Again there was no evidence of hybridization.

Four XX true hermaphrodites were studied by Damiani et al. (1990). Y-specific sequences including ZFY could not be identified in any of the four. The same is true in three cases of XX true hermaphroditism evaluated by Abbas et al. (1990).

Two XX true hermaphrodites were studied by Pereira et al. (1991) using probes for SRY. Both of the patients were negative for the probes. Similar data were obtained by Berkovitz et al. (1992) by use of a variety of Y-specific probes including SRY, ZFY, and centromeric pDP97, in five XX true hermaphrodites, including one with a terminal Xp deletion. Whereas sequences including SRY and ZFY were detected by Southern blotting or PCR in the patient with the Xp deletion, no Y-specific sequences were detected in the other four patients.

Nakagome et al. (1991) evaluated 25 Y-specific probes in an XX true hermaphrodite with mild gynecomastia, small penis, hypospadias, right scrotal testis, and left inguinal ovotestis. Two Y-loci were detected by PCR in this case: SRY and the proximal border of the pseudoautosomal region (PABY) (also see Palmer et al., 1989).

The same two loci were detected in 3 of 30 XX true hermaphrodites evaluated by McElreavey et al. (1992) (in two of those cases, SRY was localized to terminal Xp by in situ hybridization; this is consistent with X–Y interchange). Thus, although Y-DNA may occasionally be found in true hermaphroditism, this seems to be rare (the methods described above do not rule out the possibility of cryptic Y-bearing cell lines in gonadal tissue, however).

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Time series classification (TSC) has attracted significant interest over the past decade. A lot of TSC methods have been proposed. Among these TSC methods, shapelet based methods are promising for they are interpretable, more accurate, and faster than other methods. For this, a lot of acceleration strategies are proposed. However, the accuracies of speedup methods are not ideal. To address these problems, an XGBoost classifier based on shapelet features (XG-SF) is proposed in this work. In XG-SF, an XGBoost classifier based on shapelet features is used to improve classification accuracy. Our experimental results demonstrate that XG-SF is faster than the state-of-the-art classifiers and the classification accuracy rate is also improved to a certain extent.Biochemical and Biophysical Research Communications

Volume 78, Issue 2, 23 September 1977, Pages 655-662

Radioimmune assay for the Xg(a) surface antigen at the individual red cell level

Author links open overlay panelPaulSzaboMarcelloSiniscalco

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https://doi.org/10.1016/0006-291X(77)90229-7Get rights and content

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An indirect radioimmune assay has been successfully used for the detection of the Xg(a) antigen on the surface of individual human red blood cells. The assay requires only microvolumes of reagents, is highly sensitive, and is equally reliable with fresh blood samples and with red blood cells stored in liquid nitrogen. The method has been used to estimate the number of Xg(a) binding sites. It may be useful to screen for quantitative isoalleles, as well as to investigate the alleged lack of participation of the Xg-locus in the inactivation of the X-chromosome.Optik

Volume 125, Issue 14, July 2014, Pages 3637-3640

Simulative analysis of co-existing 2.5 G/10 G asymmetric XG-PON system using RZ and NRZ data formats

Author links open overlay panelAmandeepKauraAnuSheetalb

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https://doi.org/10.1016/j.ijleo.2014.01.074Get rights and content

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In this paper, a fiber optic communication system has been employed using co-existing 10 G/2.5 G asymmetric gigabit passive optical network (XG-PON) architecture. In this system, bidirectional optical fiber has been used for upstream and downstream data transmission. The system performance has been investigated for non-return-to-zero (NRZ) and return-to-zero (RZ) data formats operating at varying bit rates by varying the length of the fiber for analyzing the feasibility of this co-existence. The results have been compared for NRZ and RZ formats for upstream and downstream data in terms of Q value and eye opening. It is observed that RZ modulation format is superior as compared to conventional NRZ format and the faithful transmission of signal has been carried up to 90 km at 1577 nm for downstream and 140 km at 1270 nm for upstream.Biochemical and Biophysical Research Communications

Volume 60, Issue 3, 8 October 1974, Pages 958-964

Localization of the xg allotypic determinants, in which carbohydrate structures take part, to the separable parts of the rabbit IgG molecule

Author links open overlay panelChristianLe QuernJacquesOudin

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https://doi.org/10.1016/0006-291X(74)90407-0Get rights and content

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Enzyme-immunologic and radio-immunologic techniques made it possible to localize the determinants responsible for the xg allotypic specificity (in which carbohydrate structures are involved) to the heavy polypeptide chains and the Fc fragment of rabbit IgG, but not to the light chains nor the Fab fragment, and in part to the F(ab′)2 fragment obtained by pepsin digestion. The relationship between the xg and the e14 allotypic patterns, to date always found together in the same individuals, is discussed in light of these results.Wear

Volume 302, Issues 1–2, April–May 2013, Pages 854-862

Effects of the sub-zero treatment condition on microstructure, mechanical behavior and wear resistance of W9Mo3Cr4V high speed steel

Author links open overlay panelX.G.YanabD.Y.Lib

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https://doi.org/10.1016/j.wear.2012.12.037Get rights and content

Abstract

The sub-zero treatment can improve mechanical properties and wear resistance of many metallic materials and the improvement is largely affected by the sub-zero treatment condition. In this study, samples of W9Mo3Cr4V (W9) high speed steel (HSS) were treated at various sub-zero temperatures before and after tempering, respectively. The main objective of this work is to investigate the effect of the sub-zero treatment condition on mechanical properties and wear resistance of the W9 HSS and correlate it to variations in microstructure. Microstructures of the treated samples were characterized with electron microscopy (SEM and TEM), and corresponding properties, including hardness, impact toughness and wear resistance, were evaluated. It was demonstrated that the mechanical properties of the cryogenically treated samples were superior to those of conventionally treated ones. The cryogenically treated samples with subsequent tempering performed better than cryogenically treated samples that experienced prior tempering. The lower temperatures for sub-zero treatment were more effective in improving the mechanical properties. The life of W9 HSS taps in cutting 30CrMnTi steel was assessed, which showed a trend similar to that observed during wear testing. Efforts are made to clarify possible mechanisms responsible for the improvements.The absorption spectra of the near-infrared and ultraviolet bands of ReF6 have been recorded with a commercial spectrophotometer. The vibronic assignments previously published by different authors are critically revised. A non-perturbative method has been used to calculate the linear Jahn–Teller levels for the ν5 mode in the ground electronic state. Some new vibronic parameter values are derived. The ν5 linear Jahn–Teller parameter in the XG′g electronic state is found to be D5=0.103(9). The ultraviolet absorption spectrum has enabled us to determine relatively accurate values of the crystal-field (10Dq) and spin-orbit (ζd) parameters.Dynamic and steady shear rheometry and differential scanning calorimetry (DSC) were used to investigate effects of xyloglucan (XG) on gelatinization and retrogradation of tapioca starch (TS). The viscosity of TS/XG pastes immediately after gelatinization increased with increasing XG content at the total polysaccharide concentration of 3.5%. Gelatinized TS alone showed pseudoplastic flow at low shear rates and dilatant behavior at higher shear rates (about >1 s−1), while mixtures with XG did not show dilatancy. Mechanical spectra of TS pastes containing XG were more liquid-like than those of TS pastes without XG. XG provides shear stability to the TS during storage. Increases in dynamic moduli during storage at 5 °C were suppressed in the presence of XG. In contrast, the retrogradation ratio determined based on DSC increased more rapidly in the presence of XG. These results suggest that XG forms a continuous liquid phase in a mixture to impart better mechanical stability during storage but to accelerate re-ordering of starch polysaccharides by effectively reducing the amount of water available for starch.X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by failure of B-cell differentiation and hypogammaglobulinemia. In addition to being susceptible to bacterial infections, patients with XLA are also susceptible to enteroviruses. Systemic enterocytopathogenic human orphan virus (ECHO), coxsackie virus, and vaccine-related polio infections have caused severe morbidity and high mortality rates in XLA patients.

Objective

We report a 54-year-old male with molecularly defined XLA who survived wild poliomyelitis in childhood before the diagnosis of XLA.

Methods

At age 5, in 1951, the patient contracted wild polio, characterized by diarrhea and motor weakness. He subsequently developed recurrent sinusitis, bronchitis, and pneumonia, and at age 31 was found to be hypogammaglobulinemic and was started on immunoglobulin replacement. Laboratory evaluation at age 47 revealed an immunoglobulin G of 256 mg/dL, and B-cells (CD19) of 0.1%. Mutation analysis of Bruton's tyrosine kinase revealed a 26-basepair deletion between nucleotides 146 and 173 within the plextrin homology domain, resulting in a frameshift and premature termination.X-linked Agammaglobulinemia is a primary immunodeficiency caused by mutations in BTK, a tyrosine kinase essential for B lymphocytes differentiation. Patients usually have very low or absent B lymphocytes and are not able to develop humoral specific responses. Here we present a boy, diagnosed with XLA due to a mutation on the promoter region of the gene, whose phenotype is characterised by low percentage of B cells, hypogammaglobulinemia, oscillating neutropenia, antibodies responses to some antigens after vaccination and IgE-mediated allergy. Additional technology as flow cytometry was needed to demonstrate the pathological status of the variant. We focus on the idea that XLA should be suspected in males with B lymphopenia and hypogammaglobulinemia, even if they make humoral specific responses. We also highlight the importance of sequencing BTK's promoter region, as mutations on it can be disease-causing.Toll-like receptors (TLRs) are essential components of the innate immune system, and their ligands are important activators of neutrophils. Bruton's tyrosine kinase (Btk) has been reported to mediate signaling through toll-like receptors (TLRs) in many cell types, however, the role of Btk in TLR activation of neutrophils remains unclear. Impaired TLR-induced neutrophil function was found in mice with loss of Btk and in humans with TLR-signaling defects, but the integrity of TLR pathways in X-linked agammaglobulinemia (XLA) neutrophils has not been assessed. In this study LPS (TLR4) or an imidazoquinoline compound (TLR7/8) activated XLA neutrophil shedding of surface CD62L, and phosphorylated MAP kinases p38, JNK and ERK. TLR activation also induced normal respiratory burst and retarded apoptosis for XLA neutrophils, comparable to normal controls. These data demonstrate that the loss of Btk in XLA neutrophils does not impair functional responses to TLR signals.The Lancet

Volume 297, Issue 7695, 20 February 1971, Pages 371-373

ORIGINAL ARTICLES

ANOMALOUS Xg INHERITANCE WITH A PROBABLE EXPLANATION

Author links open overlay panelKarinE.BucktonabRuthSangerb

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https://doi.org/10.1016/S0140-6736(71)92210-0Get rights and content

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The peripheral blood cells of the mother of three children presented a mosaic karyotype 45,X/46,XX, the two cell lines being in the approximate proportion of 1 to 2. The mother and her husband were phenotypically Xg(a—), but two of the three children were Xg(a+). It was assumed, because of her fertility, that her gonads were, at least in part, 46,XX; and, because of the aberrant Xg inheritance, that her constitutional genotype was XgaXg but that her red cells were derived from a predominantly 45,X line. The latter presumption was supported when the karyotype of her marrow showed about 90% of the cells to be 45,X.The objective of this study was to examine the effects of dietary carbohydrases (xylanase and β-glucanase; XG), individually or in combination with phytase or acidifier on the growth performance, carcass attributes, intestinal microbial counts and morphology in broiler chickens fed a wheat-based diet. A total of 240 one-day-old male broiler chicks were randomly allocated into 4 treatment groups with 6 replicates of 10 birds each. The dietary treatments included a basal diet, the basal diet with an enzyme complex containing XG, XG plus a microbial phytase (XG + P) and XG plus acidifier (XG + A). The results indicated that feed conversion ratio (FCR) was improved in broiler chickens which received XG + A during the entire production period (1 to 35 d) of the trial (P < 0.05). The broiler chickens fed XG + P had lower feed intake compared with the control group at 29 to 35 d of age. The experimental treatments had no effect on the body weight gain of broiler chickens. In carcass traits, except for spleen (P < 0.05), the dietary treatments had no effects on the carcass characteristics of broiler chickens. The birds which received diets supplemented with XG and XG + A had a lower weight of the spleen compare with the control. Addition of XG in combination with phytase (XG + P) resulted in a decrease in ileal enumeration of Escherichia coli at 35 d of age (P < 0.05). However, dietary treatments did not alter the population of ileal Lactobacilli in broiler chickens. Supplementing carbohydrases with phytase and acidifier (XG + P and XG + A) significantly increased the intestinal villus length at 35 d of age (P < 0.05). In conclusion, the present study demonstrated that supplementation of the wheat-based diet with a combination with carbohydrases and acidifier (XG + A) improves FCR in broiler chickens. Furthermore, combinations of carbohydrases with phytase (XG + P) and with acidifier (XG + A) decrease the E. coli counts and increase the villus length in broiler chickens.

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