Intra-organ cell specific mitochondrial quantitative interactomics.

Almost every organ consists of many cell types, each with its unique functions. Proteomes of these cell types are thus unique too. But it is reasonable to assume that interactome (inter and intra molecular interactions of proteins) are also distinct since protein interactions are what ultimately carry out the function. Podocytes and tubules are two cell types within kidney with vastly different functions: podocytes envelop the blood vessels in the glomerulus and act as filters while tubules are located downstream of the glomerulus and are responsible for reabsorption of important nutrients. It has been long known that for tubules mitochondria plays an important role as they require a lot of energy to carry out their functions. In podocytes, however, it has been assumed that mitochondria might not matter as much in both normal physiology and pathology1. Here we have applied quantitative cross-linking mass spectrometry to compare mitochondrial interactomes of tubules and podocytes using a transgenic mitochondrial tagging strategy to immunoprecipitate cell-specific mitochondria directly from whole kidney. We have uncovered that mitochondrial proteomes of these cell types are quite similar, although still showing unique features that correspond to known functions, such as high energy production through TCA cycle in tubules and requirements for detoxification in podocytes which are on the frontline of filtration where they encounter toxic compounds and therefore, as a non-renewing cell type they must have ways to protect themselves from cellular toxicity. But we gained much deeper insight with the interactomics data. We were able to find pathways differentially regulated in podocytes and tubules based on changing cross-link levels and not just protein levels. Among these pathways are betaine metabolism, lysine degradation, and many others. We have also demonstrated how quantitative interactomics could be used to detect different activity levels of an enzyme even when protein abundances of it are the same between cell types. We have validated this finding with an orthogonal activity assay. Overall, this work presents a new view of mitochondrial biology for two important, but functionally distinct, cell types within the mouse kidney showing both similarities and unique features. This data can continue to be explored to find new aspects of mitochondrial biology, especially in podocytes, where mitochondria has been understudied. In the future this methodology can also be applied to other organs to uncover differences in the function of cell types.

Massive spontaneous haemoperitoneum in a post-partum patient with neurofibromatosis type 1. / Hemoperitoneo espontáneo masivo en paciente puérpera afecta de neurofibromatosis tipo 1.

Neurofibromatosis type 1 (NF-1) or von Recklinghausen's disease is a genetic, progressive, multi-system disease that predominantly affects the skin and nervous system. Vascular involvement is rare, but can have catastrophic results. Pregnant patients with this disease need careful, multidisciplinary follow up in order to control possible vascular alterations, which usually affect the kidneys. We present the case of a patient diagnosed with NF-1 who debuted with massive spontaneous hemoperitoneum in the late postoperative period of an elective Cesarean section. Spontaneous bleeding from large vessels is a rare but potentially lethal complication that can occur in patients with NF-1, and may require urgent surgical treatment.

Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) due to microtubule-associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy.

AIM: The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. METHODS: Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. RESULTS: The series consisted of five men and three women with an average age of death of 58 years (52-65 years) and average disease duration of 9 years (3-14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876-1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). CONCLUSIONS: This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.

Low frequency of Toll-like receptors 2 and 4 gene polymorphisms in Mexican patients and their association with type 2 diabetes.

Type 2 diabetes (T2D) is characterized by a chronic low-grade inflammatory state. SNP in Toll-like receptor (TLR) genes has been associated with impaired inflammatory response. We genotyped the TLR4/D299G, TLR4/T399I and TLR2/R753Q polymorphisms. Low frequency was found with no association with T2D, nevertheless the TLR2 SNP was associated with lower levels in HDL-cholesterol values.

Hidrotórax tras cateterización de vena yugular interna derecha / No disponible

No disponible

PCR use of highly conserved DNA regions for identification of Sinorhizobium meliloti.

A PCR identification method in which four primers that recognize homologous conserved regions in the Sinorhizobium meliloti genome are used was developed and tested. The regions used for identification were the nodbox 4 locus, which is located in one of the symbiotic megaplasmids, and the mucR gene, which is located in the chromosome. The new method was used to establish a collection of S. meliloti strains from polluted soils.

MucR is necessary for galactoglucan production in Sinorhizobium meliloti EFB1.

Sinorhizobium meliloti can produce two types of acidic exopolysaccharides, succinoglycan and galactoglucan, that are interchangeable for infection of alfalfa nodules. Strain SU47 and derivatives produce only succinoglycan, unless it grows under phosphate limitation or carries a mutation in either of two regulatory loci, mucR or expR. It has been proposed that MucR acts as a transcriptional repressor that blocks the expression of the exp genes responsible for galactoglucan production. Strain EFB1 simultaneously produces both exopolysaccharides. Heterologous expression of lacZ transcriptional fusions of the expE promoters has shown that genetic background is more important that promoter sequence for exp gene expression, since expE promoters from both strains are expressed at high level in EFB1 and not in SU47. We have found that mucR is present in mucoid and nonmucoid strains, and in EFB1 differs from SU47 in only one conservative amino acid change. MucR proteins from both strains are interchangeable. An mucR mutant of EFB1 cannot produce galactoglucan and does not express mucS.

Sex specific proteins and proteases present in the midguts of Anopheles albimanus (Diptera: Culicidae).

Proteins and proteases present in midgut tissues of sugar-fed Anopheles albimanus (Wiedemann) males and females were studied by 2-dimensional electrophoresis and zymograms using gelatin and hemoglobin as substrates. Protein patterns differed between sexes. Some proteins were similar in both sexes, but differed in intensity. Sex specific proteins and midgut proteases also were detected. These findings indicate the possibility of sex dependent regulation of midgut proteins and protease production.