Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition.

Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38-66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16-24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach

Effects of dynamic loading on solute transport through the human cartilage endplate

Nutrient and metabolite transport through the cartilage endplate (CEP) is important for maintaining proper disc nutrition, but the mechanisms of solute transport remain unclear. One unresolved issue is the role of dynamic loading. In comparison to static loading, dynamic loading is thought to enhance transport by increasing convection. However, the CEP has a high resistance to fluid flow, which could limit solute convection. Here we measure solute transport through site-matched cadaveric human lumbar CEP tissues under static vs. dynamic loading, and we determine how the degree of transport enhancement from dynamic loading depends on CEP porosity and solute size. We found that dynamic loading significantly increased small and large solute transport through the CEP: on average, dynamic loading increased the transport of sodium fluorescein (376 Da) by a factor of 1.85 ± 0.64 and the transport of a large dextran (4000 Da) by a factor of 4.97 ± 3.05. Importantly, CEP porosity (0.65 ± 0.07; range: 0.47-0.76) strongly influenced the degree of transport enhancement. Specifically, for both solutes, transport enhancement was greater for CEPs with low porosity than for CEPs with high porosity. This is because the CEPs with low porosity were susceptible to larger improvements in fluid flow under dynamic loading. The CEP becomes less porous and less hydrated with aging and as disc degeneration progresses. Together, these findings suggest that as those changes occur, dynamic loading has a greater effect on solute transport through the CEP compared to static loading, and thus may play a larger role in disc nutrition

Air pollution and the microvasculature: A cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA)

10.1371/journal.pmed.1000372PLoS Medicine711

Igbo-English intrasentential codeswitching and the Matrix Language Frame model

This paper uses data from Igbo-English intrasentential codeswitching involving mixed nominal expressions to test the Matrix Language Frame (MLF) model. The MLF model is one of the most highly influential frameworks used in the study of grammatical aspects of codeswitching. Three principles associated with it, the Matrix Language Principle, the Asymmetry Principle and the Uniform Structure Principle, were tested on data collected from informal conversations by educated adult Igbo-English bilinguals resident in Port Harcourt. The results of the analyses suggest general support for the three principles and for identifying Igbo-English as a “classic” case of codeswitching

Diversity in African languages: Selected papers from the 46th Annual Conference on African Linguistics

Diversity in African Languages contains a selection of revised papers from the 46th Annual Conference on African Linguistics, held at the University of Oregon. Most chapters focus on single languages, addressing diverse aspects of their phonology, morphology, semantics, syntax, information structure, or historical development. These chapters represent nine different genera: Mande, Gur, Kwa, Edoid, Bantu, Nilotic, Gumuzic, Cushitic, and Omotic. Other chapters investigate a mix of languages and families, moving from typological issues to sociolinguistic and inter-ethnic factors that affect language and accent switching. Some chapters are primarily descriptive, while others push forward the theoretical understanding of tone, semantic problems, discourse related structures, and other linguistic systems. The papers on Bantu languages reflect something of the internal richness and continued fascination of the family for linguists, as well as maturation of research on the family. The distribution of other papers highlights the need for intensified research into all the language families of Africa, including basic documentation, in order to comprehend linguistic diversities and convergences across the continent. In this regard, the chapter on Daats’íin (Gumuzic) stands out as the first-ever published article on this hitherto unknown and endangered language found in the Ethiopian-Sudanese border lands

Diversity in African languages: Selected papers from the 46th Annual Conference on African Linguistics

Diversity in African Languages contains a selection of revised papers from the 46th Annual Conference on African Linguistics, held at the University of Oregon. Most chapters focus on single languages, addressing diverse aspects of their phonology, morphology, semantics, syntax, information structure, or historical development. These chapters represent nine different genera: Mande, Gur, Kwa, Edoid, Bantu, Nilotic, Gumuzic, Cushitic, and Omotic. Other chapters investigate a mix of languages and families, moving from typological issues to sociolinguistic and inter-ethnic factors that affect language and accent switching. Some chapters are primarily descriptive, while others push forward the theoretical understanding of tone, semantic problems, discourse related structures, and other linguistic systems. The papers on Bantu languages reflect something of the internal richness and continued fascination of the family for linguists, as well as maturation of research on the family. The distribution of other papers highlights the need for intensified research into all the language families of Africa, including basic documentation, in order to comprehend linguistic diversities and convergences across the continent. In this regard, the chapter on Daats’íin (Gumuzic) stands out as the first-ever published article on this hitherto unknown and endangered language found in the Ethiopian-Sudanese border lands

Diversity in African languages: Selected papers from the 46th Annual Conference on African Linguistics

Diversity in African Languages contains a selection of revised papers from the 46th Annual Conference on African Linguistics, held at the University of Oregon. Most chapters focus on single languages, addressing diverse aspects of their phonology, morphology, semantics, syntax, information structure, or historical development. These chapters represent nine different genera: Mande, Gur, Kwa, Edoid, Bantu, Nilotic, Gumuzic, Cushitic, and Omotic. Other chapters investigate a mix of languages and families, moving from typological issues to sociolinguistic and inter-ethnic factors that affect language and accent switching. Some chapters are primarily descriptive, while others push forward the theoretical understanding of tone, semantic problems, discourse related structures, and other linguistic systems. The papers on Bantu languages reflect something of the internal richness and continued fascination of the family for linguists, as well as maturation of research on the family. The distribution of other papers highlights the need for intensified research into all the language families of Africa, including basic documentation, in order to comprehend linguistic diversities and convergences across the continent. In this regard, the chapter on Daats’íin (Gumuzic) stands out as the first-ever published article on this hitherto unknown and endangered language found in the Ethiopian-Sudanese border lands

Diversity in African languages: Selected papers from the 46th Annual Conference on African Linguistics

Diversity in African Languages contains a selection of revised papers from the 46th Annual Conference on African Linguistics, held at the University of Oregon. Most chapters focus on single languages, addressing diverse aspects of their phonology, morphology, semantics, syntax, information structure, or historical development. These chapters represent nine different genera: Mande, Gur, Kwa, Edoid, Bantu, Nilotic, Gumuzic, Cushitic, and Omotic. Other chapters investigate a mix of languages and families, moving from typological issues to sociolinguistic and inter-ethnic factors that affect language and accent switching. Some chapters are primarily descriptive, while others push forward the theoretical understanding of tone, semantic problems, discourse related structures, and other linguistic systems. The papers on Bantu languages reflect something of the internal richness and continued fascination of the family for linguists, as well as maturation of research on the family. The distribution of other papers highlights the need for intensified research into all the language families of Africa, including basic documentation, in order to comprehend linguistic diversities and convergences across the continent. In this regard, the chapter on Daats’íin (Gumuzic) stands out as the first-ever published article on this hitherto unknown and endangered language found in the Ethiopian-Sudanese border lands

Diversity in African languages: Selected papers from the 46th Annual Conference on African Linguistics

Diversity in African Languages contains a selection of revised papers from the 46th Annual Conference on African Linguistics, held at the University of Oregon. Most chapters focus on single languages, addressing diverse aspects of their phonology, morphology, semantics, syntax, information structure, or historical development. These chapters represent nine different genera: Mande, Gur, Kwa, Edoid, Bantu, Nilotic, Gumuzic, Cushitic, and Omotic. Other chapters investigate a mix of languages and families, moving from typological issues to sociolinguistic and inter-ethnic factors that affect language and accent switching. Some chapters are primarily descriptive, while others push forward the theoretical understanding of tone, semantic problems, discourse related structures, and other linguistic systems. The papers on Bantu languages reflect something of the internal richness and continued fascination of the family for linguists, as well as maturation of research on the family. The distribution of other papers highlights the need for intensified research into all the language families of Africa, including basic documentation, in order to comprehend linguistic diversities and convergences across the continent. In this regard, the chapter on Daats’íin (Gumuzic) stands out as the first-ever published article on this hitherto unknown and endangered language found in the Ethiopian-Sudanese border lands