Purpose Proximal interphalangeal (PIP) joint fracture-dislocations are complex injuries, and successful surgical treatment can be challenging. The hamate appears to be an appropriate graft based on ...its general shape and dimensions. The purpose of this study was to evaluate the rationale and suitability of the hamate as an autograft for proximal interphalangeal joint fracture-dislocations and to determine the inherent stability of the donor site after graft harvesting. Methods Fresh-frozen cadaveric hand specimens were used to evaluate the hamate as a suitable graft source for defects of the middle phalanx based on macroscopic, radiographic, and biomechanical properties. Radiographic measurements were made of the articular contours of the hamate and the base of middle phalanx of digits 2 through 5. Hemicondylar hamate replacement arthroplasty (HHRA) was performed in cadavers for defects created in the middle phalanges. Biomechanical stability testing of the hamate-metacarpal joint was then assessed in additional specimens before and after HHRA. Fluoroscopic examination with a 22.2-N load applied in a 45° dorsal-proximal direction was used to assess stability of the carpometacarpal joints. A servohydraulic testing machine was then used to determine the amount of translation induced with a similarly directed force before and after harvesting of the hamate graft. Results The cadaveric HHRA reconstructions restored joint stability with no tendency to subluxate. Radiographic measurement showed that the hamate has a central ridge and bicondylar facet with articular contours that are similar to the base of the middle phalanx. The removal of a central portion of the hamate did not induce dislocation or create obvious clinical instability of the carpometacarpal joint. Conclusions The HHRA technique is used for treatment of fracture-dislocations of the proximal interphalangeal joint. This study demonstrated the suitability of using the dorsal portion of the hamate as an osteochondral autograft for middle phalangeal base fractures; the technique creates minimal donor site morbidity. Type of study/level of evidence Therapeutic IV.
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GEOZS, NUK, OILJ, SBCE, UL
The recent discovery of CD4^sup +^ T cells characterized by secretion of interleukin (IL)-17 (T^sub H^17 cells) and the naturally occurring regulatory FOXP3^sup +^ CD4 T cell (nT^sub reg^) has had a ...major impact on our understanding of immune processes not readily explained by the T^sub H^1/T^sub H^2 paradigm. T^sub H^17 and nT^sub reg^ cells have been implicated in the pathogenesis of human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and psoriasis. Our recent data and the work of others demonstrated that transforming growth factor-β (TGF-β) and IL-6 are responsible for the differentiation of naive mouse T cells into T^sub H^17 cells, and it has been proposed that IL-23 may have a critical role in stabilization of the T^sub H^17 phenotype. A second pathway has been discovered in which a combination of TGF-β and IL-21 is capable of inducing differentiation of mouse T^sub H^17 cells in the absence of IL-6 (refs 6-8). However, TGF-β and IL-6 are not capable of differentiating human T^sub H^17 cells and it has been suggested that TGF-β may in fact suppress the generation of human T^sub H^17 cells. Instead, it has been recently shown that the cytokines IL-1β, IL-6 and IL-23 are capable of driving IL-17 secretion in short-term CD4^sup +^ T cell lines isolated from human peripheral blood, although the factors required for differentiation of naive human CD4 to T^sub H^17 cells are still unknown. Here we confirm that whereas IL-1β and IL-6 induce IL-17A secretion from human central memory CD4^sup +^ T cells, TGF-β and IL-21 uniquely promote the differentiation of human naive CD4^sup +^ T cells into T^sub H^17 cells accompanied by expression of the transcription factor RORC2. These data will allow the investigation of this new population of T^sub H^17 cells in human inflammatory disease. PUBLICATION ABSTRACT
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The recent discovery of CD4 super(+) T cells characterized by secretion of interleukin (IL)-17 (T sub(H)17 cells) and the naturally occurring regulatory FOXP3 super(+) CD4 T cell (nT sub(reg)) has ...had a major impact on our understanding of immune processes not readily explained by the T sub(H)1/T sub(H)2 paradigm. T sub(H)17 and nT sub(reg) cells have been implicated in the pathogenesis of human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and psoriasis. Our recent data and the work of others demonstrated that transforming growth factor-beta (TGF-beta) and IL-6 are responsible for the differentiation of naive mouse T cells into T sub(H)17 cells, and it has been proposed that IL-23 may have a critical role in stabilization of the T sub(H)17 phenotype. A second pathway has been discovered in which a combination of TGF-beta and IL-21 is capable of inducing differentiation of mouse T sub(H)17 cells in the absence of IL-6. However, TGF-beta and IL-6 are not capable of differentiating human T sub(H)17 cells and it has been suggested that TGF-beta may in fact suppress the generation of human T sub(H)17 cells. Instead, it has been recently shown that the cytokines IL-1beta, IL-6 and IL-23 are capable of driving IL-17 secretion in short-term CD4 super(+) T cell lines isolated from human peripheral blood, although the factors required for differentiation of naive human CD4 to T sub(H)17 cells are still unknown. Here we confirm that whereas IL-1beta and IL-6 induce IL-17A secretion from human central memory CD4 super(+) T cells, TGF- beta and IL-21 uniquely promote the differentiation of human naive CD4 super(+) T cells into T sub(H)17 cells accompanied by expression of the transcription factor RORC2. These data will allow the investigation of this new population of T sub(H)17 cells in human inflammatory disease.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The recent discovery of CD4+ T cells characterized by secretion of interleukin (IL)-17 (TH17 cells) and the naturally occurring regulatory FOXP3+ CD4 T cell (nTreg) has had a major impact on our ...understanding of immune processes not readily explained by the TH1/TH2 paradigm. TH17 and nTreg cells have been implicated in the pathogenesis of human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and psoriasis. Our recent data and the work of others demonstrated that transforming growth factor- (TGF- ) and IL-6 are responsible for the differentiation of naive mouse T cells into TH17 cells, and it has been proposed that IL-23 may have a critical role in stabilization of the TH17 phenotype. A second pathway has been discovered in which a combination of TGF- and IL-21 is capable of inducing differentiation of mouse TH17 cells in the absence of IL-6 (refs 6-8). However, TGF- and IL-6 are not capable of differentiating human TH17 cells and it has been suggested that TGF- may in fact suppress the generation of human TH17 cells. Instead, it has been recently shown that the cytokines IL-1 , IL-6 and IL-23 are capable of driving IL-17 secretion in short-term CD4+ T cell lines isolated from human peripheral blood, although the factors required for differentiation of naive human CD4 to TH17 cells are still unknown. Here we confirm that whereas IL-1 and IL-6 induce IL-17A secretion from human central memory CD4+ T cells, TGF- and IL-21 uniquely promote the differentiation of human naive CD4+ T cells into TH17 cells accompanied by expression of the transcription factor RORC2. These data will allow the investigation of this new population of TH17 cells in human inflammatory disease.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Periodical cicadas live 13 or 17 years underground as nymphs, then emerge in synchrony as adults to reproduce. Developmentally synchronized populations called broods rarely coexist, with one dominant ...brood locally excluding those that emerge in off years. Twelve modern 17-year cicada broods are believed to have descended from only three ancestral broods following the last glaciation. The mechanisms by which these daughter broods overcame exclusion by the ancestral brood to synchronously emerge in a different year, however, are elusive. Here, we demonstrate that temporal variation in the population density of generalist predators can allow intermittent opportunities for new broods to invade, even though a single brood remains dominant most of the time. We show that this mechanism is consistent, in terms of the type and frequency of brood replacements, with the distribution of periodical cicada broods throughout North America today. Although we investigate one particularly charismatic case study, the mechanisms involved (competitive exclusion, Allee effects, trait variation, predation, and temporal variability) are ubiquitous and could contribute to patterns of species diversity in a range of systems.
The pathogenic mold Aspergillus fumigatus is the most frequent infectious cause of death in severely immunocompromised individuals such as leukemia and bone marrow transplant patients. Germination of ...inhaled conidia (asexual spores) in the host is critical for the initiation of infection, but little is known about the underlying mechanisms of this process.
To gain insights into early germination events and facilitate the identification of potential stage-specific biomarkers and vaccine candidates, we have used quantitative shotgun proteomics to elucidate patterns of protein abundance changes during early fungal development. Four different stages were examined: dormant conidia, isotropically expanding conidia, hyphae in which germ tube emergence has just begun, and pre-septation hyphae. To enrich for glycan-linked cell wall proteins we used an alkaline cell extraction method. Shotgun proteomic resulted in the identification of 375 unique gene products with high confidence, with no evidence for enrichment of cell wall-immobilized and secreted proteins. The most interesting discovery was the identification of 52 proteins enriched in dormant conidia including 28 proteins that have never been detected in the A. fumigatus conidial proteome such as signaling protein Pil1, chaperones BipA and calnexin, and transcription factor HapB. Additionally we found many small, Aspergillus specific proteins of unknown function including 17 hypothetical proteins. Thus, the most abundant protein, Grg1 (AFUA_5G14210), was also one of the smallest proteins detected in this study (M.W. 7,367). Among previously characterized proteins were melanin pigment and pseurotin A biosynthesis enzymes, histones H3 and H4.1, and other proteins involved in conidiation and response to oxidative or hypoxic stress. In contrast, expanding conidia, hyphae with early germ tubes, and pre-septation hyphae samples were enriched for proteins responsible for housekeeping functions, particularly translation, respiratory metabolism, amino acid and carbohydrate biosynthesis, and the tricarboxylic acid cycle.
The observed temporal expression patterns suggest that the A. fumigatus conidia are dominated by small, lineage-specific proteins. Some of them may play key roles in host-pathogen interactions, signal transduction during conidial germination, or survival in hostile environments.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
B-1 cells constitute a distinct B cell subset with characteristic phenotypic and functional features. B-1 cells are highly represented among peritoneal lymphocytes; substantial numbers of B-1 cells ...are also located within splenic tissue. Here a number of differences in transcription factor and gene expression were identified that separate peritoneal B-1 and splenic B-2 cells, and then splenic B-1 cells obtained from immunoglobulin transgenic mice were tested for these parameters. Splenic B-1 cells resembled splenic B-2 cells rather than peritoneal B-1 cells in terms of nuclear expression of DNA-binding STAT3, CREB, and PU.1, with respect to transcriptional activation of IL-10, and in the failure to enter cell cycle in response to PMA. Splenic B-1 cells (B-1S) appear to constitute a unique population of B-1 cells, which, while sharing with peritoneal B-1 cells (B-1P) certain phenotypic features, differ from them in transcription factor and gene expression and in signaling for cell cycle progression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
![IL-21 and TGF-[beta] are re...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0028-0836/small "IL-21 and TGF-[beta] are required for differentiation of human T^sub H^17 cells")
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