Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.

Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.

Bilateral asymmetric traumatic hip dislocation associated with epiphysiolysis of the femoral head in an adolescent patient.

Background: Bilateral asymmetric hip dislocation is uncommon in childhood, even more when associated with epiphyseal slippage, leading to catastrophic complications of the affected joints, requiring additional surgical interventions, and increasing patient morbidity. In this article, we present the case of a 15 years-old patient with a post-traumatic bilateral hip dislocation with epiphyseal slippage, initially managed with open reduction and fixation, with subsequent need of total hip arthroplasty. Afterward, the patient presented satisfactory outcomes. Conclusion: Hip dislocation associated with transphyseal fracture is an injury that leads to joint destruction, and despite timely management, the prognosis is poor; however, efforts should be made to provide opportune care to obtain the best outcome.

Banded RYGB Ring Slippage Endoscopic Removal with Self-expandable Stents: a Comparative Study Between Metallic and Plastic One.

PURPOSE: Banded Roux-en-Y gastric bypass (RYGB) was a common bariatric procedure in the 2000s, and the ring slippage is one of its late adverse events. Both plastic and metallic stents have been reported as adjunct methods to induce erosion and facilitate endoscopic removal of the ring. OBJECTIVE: To compare the safety and effectiveness of self-expanding metallic stents (SEMS) and plastic stents (SEPS) to treat ring slippage. MATERIALS AND METHODS: We conducted a retrospective longitudinal study analyzing consecutive patients with ring dysfunction treated with stents plus endoscopic removal. RESULTS: Ninety patients were enrolled (36 SEMS vs. 54 SEPS). The mean age was 48.56 ± 13.07 and 45.6 ± 12.1 in the SEMS and SEPS groups, respectively. All patients had band slippage, but 24 from SEMS group and 23 from SEPS group had further complications. There were more complications in metallic stent concerning mean absolute number of therapy-related adverse events (1.33 ± 0.48 vs. 1.72 ± 0.5, p > 0.05) and time until erosion (14.9 ± 1.6 vs. 13.8 ± 1.4 days, p > 0.05). Female sex and age > 41 years old correlated with longer time to band erosion and higher incidence of adverse events in SEMS patients. In SEPS group, only female sex was a risk factor for adverse events. CONCLUSION: Both procedures were efficient at inducing band erosion with similar safety profiles. Older and female patients are at a higher risk of treatment-related adverse events, especially those receiving SEMS.

Long non-coding RNA NORAD upregulation induced by airborne particulate matter (PM10) exposure leads to aneuploidy in A549 lung cells.

Air pollution is a worldwide problem that affects human health predominantly in the largest cities. Particulate matter of 10 µm or less in diameter (PM10) is considered a risk factor for multiple diseases, including lung cancer. The long non-coding RNA NORAD and the components of the spindle assembly checkpoint (SAC) ensure proper chromosomal segregation. Alterations in the SAC cause aneuploidy, a feature associated with carcinogenesis. In this study, we demonstrated that PM10 treatment increased the expression levels of NORAD as well as those of SAC components mitotic arrest deficient 1 (MAD1L1), mitotic arrest deficient 2 (MAD2L1), BubR1 (BUB1B), aurora B (AURKB), and survivin (BIRC5) in the lung A549 cell line. We also demonstrated that MAD1L1, MAD2L1, and BUB1B expression levels were reduced when cells were transfected with small interfering RNAs (siRNAs) against NORAD. Interestingly, the expression levels of AURKB and BIRC5 (survivin) were not affected by transfection with NORAD siRNAs. Cells treated with PM10 exhibited a decrease in mitotic arrest and an increase in micronuclei frequency in synchronized A549 cells. PM10 exposure induced aneuploidy events as a result of SAC deregulation. We also observed a reduction in the protein levels of Pumilio 1 after PM10 treatment. Our results provide novel clues regarding the effect of PM10 in the generation of chromosomal instability, a phenotype observed in lung cancer cells.

Mycobacterium tuberculosis and M. bovis BCG Moreau Fumarate Reductase Operons Produce Different Polypeptides That May Be Related to Non-canonical Functions.

Tuberculosis is a world widespread disease, caused by Mycobacterium tuberculosis (M.tb). Although considered an obligate aerobe, this organism can resist life-limiting conditions such as microaerophily mainly due to its set of enzymes responsible for energy production and coenzyme restoration under these conditions. One of these enzymes is fumarate reductase, an heterotetrameric complex composed of a catalytic (FrdA), an iron-sulfur cluster (FrdB) and two transmembrane (FrdC and FrdD) subunits involved in anaerobic respiration and important for the maintenance of membrane potential. In this work, aiming to further characterize this enzyme function in mycobacteria, we analyzed the expression of FrdB-containing proteins in M.tb and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) Moreau, the Brazilian vaccine strain against tuberculosis. We identified three isoforms in both mycobacteria, two of them corresponding to the predicted encoded polypeptides of M.tb (27 kDa) and BCG Moreau (40 kDa) frd sequences, as due to an insertion on the latter's operon a fused FrdBC protein is expected. The third 52 kDa band can be explained by a transcriptional slippage event, typically occurring when mutation arises in a repetitive region within a coding sequence, thought to reduce its impact allowing the production of both native and variant forms. Comparative modeling of the M.tb and BCG Moreau predicted protein complexes allowed the detection of subtle overall differences, showing a high degree of structure and maybe functional resemblance among them. Axenic growth and macrophage infection assays show that the frd locus is important for proper bacterial development in both scenarios, and that both M.tb's and BCG Moreau's alleles can partially revert the hampered phenotype of the knockout strain. Altogether, our results show that the frdABCD operon of Mycobacteria may have evolved to possess other yet non-described functions, such as those necessary during aerobic logarithmic growth and early stage steps of infection.

Airborne particulate matter induces mitotic slippage and chromosomal missegregation through disruption of the spindle assembly checkpoint (SAC).

Particulate matter (PM) is a risk factor for lung cancer development and chromosomal missegregation and cell cycle disruptions are key cellular events that trigger tumorigenesis. We aimed to study the effect of PM10 (PM with an aerodynamic diameter ≤10 µm) on mitotic arrest and chromosomal segregation, evaluating the spindle assembly checkpoint (SAC) protein dynamics in the human lung A549 adenocarcinoma cell line. For this purpose, synchronized cells were exposed to PM10 for 24 h to obtain the frequency of micronucleated (MN) and trinucleated (TN) cells. Then, the efficiency of the mitotic arrest after PM10 exposure was analyzed. To elucidate the effect of PM10 in chromosomal segregation, the levels and subcellular localization of essential SAC proteins were evaluated. Results indicated that A549 cells exposed to PM10 exhibited an increase in MN and TN cells and a decrease in mitotic indexes and G2/M phase. A549 cells treated with PM10 showed reduced protein levels of MDC1 and NEK2 (38% and 35% respectively), which is required for MAD2 recruitment to kinetochores, MAD2 and BUBR1, effectors of the SAC (25% and 18% respectively), and CYCLIN B1, required during G2/M phase (35%). Besides, PM10 exposure increase the levels of AURORA B and SURVIVIN, required for SAC activation through chromosome-microtubule attachment errors (85% and 74% respectively). We suggest that PM10 causes mitotic slippage due to alterations in MAD2 localization. Thus, PM10 causes inadequate chromosomal segregation and deficient mitotic arrest by altering SAC protein levels, predisposing A549 cells to chromosomal instability, a common feature observed in cancer.

Revisiting SEPT7 and the slippage of ß-strands in the septin family.

Septins are GTP-binding proteins that will often spontaneously assemble into filaments. In some species, particularly budding yeast, it is well known that these are capable of associating with membranes in order to fulfill their cellular role as a component of the cytoskeleton. Different from other human septins, SEPT7 appears to be unique in that it is an essential component of all hetero-oligomeric complexes described to date. As a step towards understanding the molecular basis of filament assembly, here we present two high-resolution structures of the SEPT7 GTPase domain complexed with GDP. One of these reveals a previously unreported coordination for the magnesium ion involving four water molecules and only a tenuous connection to the protein. The higher resolution structures provide unambiguous insight into the interactions at the G-interface where a structural motif based on an antiparallel ß-bridge allows for the rationalization of why some septins show nucleotide-dependent ß-strand slippage and others do not.

Tractor perfomance as a function of speed and seeder’s tire inflation pressure / Desempenho de trator em função da velocidade e da pressão de inflação dos pneus da semeadora

The performance of agricultural tractors under field conditions results from the interaction between tire and wheel affected by displacement speed. This work was developed to assess the performance of an agricultural tractor under different seeder's tire inflation pressure (518; 483 and 414kPa) and in two different gears providing speeds of 3.0 and 6.0km h-1. The experiment was performed at Jaboticabal Campus of São Paulo State University (UNESP). The experimental design used was entirely randomized in a 2-factor factorial design (3x2) with four replications. The draft force was influenced by the gear as well as by the required power; however, tire inflation pressure in the seeder did not change these parameters. Also, fuel consumption was influenced only by the tractor gear. Energy consumption was greater as speed increased, caused by gear shifting. The displacement speed was greater for the 518kPa pressure due to a lesser slippage in the seeder under this pressure. Tractor slippage did not change.

O desempenho de tratores agrícolas em condições de campo resulta da interação entre pneu e rodado, influenciado pela velocidade de deslocamento. O objetivo deste trabalho foi avaliar o desempenho de um trator agrícola sob diferentes pressões de inflação dos pneus da semeadora (518, 483, and 414kPa) e em duas marchas que proporcionaram velocidades de 3,0 e 6,0km h-1. O experimento foi realizado no campus de Jaboticabal da Universidade Estadual Paulista (UNESP). O delineamento experimental utilizado foi fatorial inteiramente casualizado (3x2), com quatro repetições. A força de tração foi influenciada pela marcha e pela potência exigida; no entanto, a pressão de inflação do pneu da semeadora não alterou esses parâmetros. Além disso, o consumo de combustível foi influenciado apenas pela marcha do trator. O consumo de energia foi maior com o aumento da velocidade, ocasionada pela mudança de marcha. A velocidade de deslocamento foi maior para a pressão de 518kPa, em razão da menor patinagem da semeadora promovida por essa pressão. A patinagem do trator não foi alterada pelos fatores testados.

Tractor perfomance as a function of speed and seeder’s tire inflation pressure

The performance of agricultural tractors under field conditions results from the interaction between tire and wheel affected by displacement speed. This work was developed to assess the performance of an agricultural tractor under different seeder's tire inflation pressure (518; 483 and 414kPa) and in two different gears providing speeds of 3.0 and 6.0km h-1. The experiment was performed at Jaboticabal Campus of São Paulo State University (UNESP). The experimental design used was entirely randomized in a 2-factor factorial design (3x2) with four replications. The draft force was influenced by the gear as well as by the required power; however, tire inflation pressure in the seeder did not change these parameters. Also, fuel consumption was influenced only by the tractor gear. Energy consumption was greater as speed increased, caused by gear shifting. The displacement speed was greater for the 518kPa pressure due to a lesser slippage in the seeder under this pressure. Tractor slippage did not change.

O desempenho de tratores agrícolas em condições de campo resulta da interação entre pneu e rodado, influenciado pela velocidade de deslocamento. O objetivo deste trabalho foi avaliar o desempenho de um trator agrícola sob diferentes pressões de inflação dos pneus da semeadora (518, 483, and 414kPa) e em duas marchas que proporcionaram velocidades de 3,0 e 6,0km h-1. O experimento foi realizado no campus de Jaboticabal da Universidade Estadual Paulista (UNESP). O delineamento experimental utilizado foi fatorial inteiramente casualizado (3x2), com quatro repetições. A força de tração foi influenciada pela marcha e pela potência exigida; no entanto, a pressão de inflação do pneu da semeadora não alterou esses parâmetros. Além disso, o consumo de combustível foi influenciado apenas pela marcha do trator. O consumo de energia foi maior com o aumento da velocidade, ocasionada pela mudança de marcha. A velocidade de deslocamento foi maior para a pressão de 518kPa, em razão da menor patinagem da semeadora promovida por essa pressão. A patinagem do trator não foi alterada pelos fatores testados.

Tractor perfomance as a function of speed and seeders tire inflation pressure

The performance of agricultural tractors under field conditions results from the interaction between tire and wheel affected by displacement speed. This work was developed to assess the performance of an agricultural tractor under different seeder's tire inflation pressure (518; 483 and 414kPa) and in two different gears providing speeds of 3.0 and 6.0km h-1. The experiment was performed at Jaboticabal Campus of São Paulo State University (UNESP). The experimental design used was entirely randomized in a 2-factor factorial design (3x2) with four replications. The draft force was influenced by the gear as well as by the required power; however, tire inflation pressure in the seeder did not change these parameters. Also, fuel consumption was influenced only by the tractor gear. Energy consumption was greater as speed increased, caused by gear shifting. The displacement speed was greater for the 518kPa pressure due to a lesser slippage in the seeder under this pressure. Tractor slippage did not change.

O desempenho de tratores agrícolas em condições de campo resulta da interação entre pneu e rodado, influenciado pela velocidade de deslocamento. O objetivo deste trabalho foi avaliar o desempenho de um trator agrícola sob diferentes pressões de inflação dos pneus da semeadora (518, 483, and 414kPa) e em duas marchas que proporcionaram velocidades de 3,0 e 6,0km h-1. O experimento foi realizado no campus de Jaboticabal da Universidade Estadual Paulista (UNESP). O delineamento experimental utilizado foi fatorial inteiramente casualizado (3x2), com quatro repetições. A força de tração foi influenciada pela marcha e pela potência exigida; no entanto, a pressão de inflação do pneu da semeadora não alterou esses parâmetros. Além disso, o consumo de combustível foi influenciado apenas pela marcha do trator. O consumo de energia foi maior com o aumento da velocidade, ocasionada pela mudança de marcha. A velocidade de deslocamento foi maior para a pressão de 518kPa, em razão da menor patinagem da semeadora promovida por essa pressão. A patinagem do trator não foi alterada pelos fatores testados.

Tractor perfomance as a function of speed and seeders tire inflation pressure

The performance of agricultural tractors under field conditions results from the interaction between tire and wheel affected by displacement speed. This work was developed to assess the performance of an agricultural tractor under different seeder's tire inflation pressure (518; 483 and 414kPa) and in two different gears providing speeds of 3.0 and 6.0km h-1. The experiment was performed at Jaboticabal Campus of São Paulo State University (UNESP). The experimental design used was entirely randomized in a 2-factor factorial design (3x2) with four replications. The draft force was influenced by the gear as well as by the required power; however, tire inflation pressure in the seeder did not change these parameters. Also, fuel consumption was influenced only by the tractor gear. Energy consumption was greater as speed increased, caused by gear shifting. The displacement speed was greater for the 518kPa pressure due to a lesser slippage in the seeder under this pressure. Tractor slippage did not change.

O desempenho de tratores agrícolas em condições de campo resulta da interação entre pneu e rodado, influenciado pela velocidade de deslocamento. O objetivo deste trabalho foi avaliar o desempenho de um trator agrícola sob diferentes pressões de inflação dos pneus da semeadora (518, 483, and 414kPa) e em duas marchas que proporcionaram velocidades de 3,0 e 6,0km h-1. O experimento foi realizado no campus de Jaboticabal da Universidade Estadual Paulista (UNESP). O delineamento experimental utilizado foi fatorial inteiramente casualizado (3x2), com quatro repetições. A força de tração foi influenciada pela marcha e pela potência exigida; no entanto, a pressão de inflação do pneu da semeadora não alterou esses parâmetros. Além disso, o consumo de combustível foi influenciado apenas pela marcha do trator. O consumo de energia foi maior com o aumento da velocidade, ocasionada pela mudança de marcha. A velocidade de deslocamento foi maior para a pressão de 518kPa, em razão da menor patinagem da semeadora promovida por essa pressão. A patinagem do trator não foi alterada pelos fatores testados.

Analysis of slipped sequences in EST projects

Slippage is an important sequencing problem that can occur in EST projects. However, very few studies have addressed this. We propose three new methods to detect slippage artifacts: arithmetic mean method, geometric mean method, and echo coverage method. Each method is simple and has two different strategies for processing sequences: suffix and subsequence. Using the 291,689 EST sequences produced in the SUCEST project, we performed comparative tests between our proposed methods and the SUCEST method. The subsequence strategy is better than the suffix strategy, because it is not anchored at the end of the sequence, so it is more flexible to find slippage at the beginning of the EST. In a comparison with the SUCEST method, the advantage of our methods is that they do not discard the majority of the sequences marked as slippage, but instead only remove the slipped artifact from the sequence. Based on our tests the echo coverage method with subsequence strategy shows the best compromise between slippage detection and ease of calibration.