Application of dye leak test for gastrointestinal tract tightness control in bariatric surgery

Проблема ожирения широко распространена как в Республике Беларусь, так и в мировом масштабе. Так по данным ВОЗ ожирением страдают 640 млн человек в мире. В Республике Беларусь в 2015–2016 г. распространенность ожирения среди взрослого населения составляла 24,5 % . Морбидное ожирение при ИМТ >40 кг/м2, или >35 кг/м2 при наличии сопутствующей патологии, часто оказывается рефрактерным к консервативным методам лечения и наиболее эффективным способом устойчивого снижения массы тела пациентов является именно хирургическое вмешательство. Среди выполняемых бариатрических операций преобладают вмешательства, предусматривающие резекцию или шунтирование желудка. Так в мире доля гастрошунтирования на петле по Ру составляет 41,9 %, рукавной резекция желудка – 32,6 %, а на долю минигастрошунтирования приходится 5,0 %. Одним из наиболее частых осложнений после перечисленных бариатрических вмешательств является несостоятельность линии швов желудка или анастомозов. После рукавной резекции желудка частота этого осложнения достигает 3,9 %, а после гастрошунтирования на петле по Ру – до 8 %. The problem of obesity is widespread both in the Republic of Belarus and on a global scale. So, according to the WHO, 640 million people in the world suffer from obesity [6]. In the Republic of Belarus in 2015–2016.rasprostranennost' ozhireniya sredi vzroslogo naseleniya sostavlyala 24,5 %. Morbidnoye ozhireniye pri IMT >40 kg/m 2 , ili >35 kg/m 2 pri nalichii soputstvuyushchey patologii, chasto okazyvayetsya refrakternym k konservativnym the prevalence of obesity among the adult population was 24.5 %. Morbid obesity with a BMI >40 kg/m 2 , or >35 kg/m 2 in the presence of concomitant pathology, is often weight loss in patients is precisely surgical intervention. Among the performed bariatric operations, interventions involving gastric resection or bypass surgery prevail. Thus, in the world, the share of gastric bypass surgery on a Roux-type loop is 41.9 %, sleeve gastrectomy is 32.6 %, and the share of mini-gastric bypass is 5.0 %. One of the most common complications after the listed bariatric procedures is the failure of the gastric suture line or anastomoses. After gastric sleeve gastrectomy, the incidence of this complication reaches 3.9 %, and after Roux-en-Y loop gastric bypass surgery – up to 8 %

TDP-43 induces p53-mediated cell death of cortical progenitors and immature neurons

TAR DNA-binding protein 43 (TDP-43) is a key player in neurodegenerative diseases including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Accumulation of TDP-43 is associated with neuronal death in the brain. How increased and disease-causing mutant forms of TDP-43 induce cell death remains unclear. Here we addressed the role of TDP-43 during neural development and show that reduced TDP-43 causes defects in neural stem/progenitor cell proliferation but not cell death. However, overexpression of wild type and TDP-43A315T proteins induce p53-dependent apoptosis of neural stem/progenitors and human induced pluripotent cell (iPS)-derived immature cortical neurons. We show that TDP-43 induces expression of the proapoptotic BH3-only genes Bbc3 and Bax, and that p53 inhibition rescues TDP-43 induced cell death of embryonic mouse, and human cortical neurons, including those derived from TDP-43G298S ALS patient iPS cells. Hence, an increase in wild type and mutant TDP-43 induces p53-dependent cell death in neural progenitors developing neurons and this can be rescued. These findings may have important implications for accumulated or mutant TDP-43 induced neurodegenerative diseases

The Lsm1-7/Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock

RNA-binding proteins (RBPs) establish the cellular fate of a transcript, but an understanding of these processes has been limited by a lack of identified specific interactions between RNA and protein molecules. Using MS2 RNA tagging, we have purified proteins associated with individual mRNA species induced by osmotic stress, STL1 and GPD1. We found members of the Lsm1-7/Pat1 RBP complex to preferentially bind these mRNAs, relative to the non-stress induced mRNAs, HYP2 and ASH1. To assess the functional importance, we mutated components of the Lsm1-7/Pat1 RBP complex and analyzed the impact on expression of osmostress gene products. We observed a defect in global translation inhibition under osmotic stress in pat1 and lsm1 mutants, which correlated with an abnormally high association of both non-stress and stress-induced mRNAs to translationally active polysomes. Additionally, for stress-induced proteins normally triggered only by moderate or high osmostress, in the mutants the protein levels rose high already at weak hyperosmosis. Analysis of ribosome passage on mRNAs through co-translational decay from the 5' end (5P-Seq) showed increased ribosome accumulation in lsm1 and pat1 mutants upstream of the start codon. This effect was particularly strong for mRNAs induced under osmostress. Thus, our results indicate that, in addition to its role in degradation, the Lsm1-7/Pat1 complex acts as a selective translational repressor, having stronger effect over the translation initiation of heavily expressed mRNAs. Binding of the Lsm1-7/Pat1p complex to osmostress-induced mRNAs mitigates their translation, suppressing it in conditions of weak or no stress, and avoiding a hyperresponse when triggered

Stress granules regulate stress-induced paraspeckle assembly

Eukaryotic cells contain a variety of RNA-protein macrocomplexes termed RNP granules. Different types of granules share multiple protein components; however, the crosstalk between spatially separated granules remains unaddressed. Paraspeckles and stress granules (SGs) are prototypical RNP granules localized exclusively in the nucleus and cytoplasm, respectively. Both granules are implicated in human diseases, such as amyotrophic lateral sclerosis. We characterized the composition of affinity-purified paraspeckle-like structures and found a significant overlap between the proteomes of paraspeckles and SGs. We further show that paraspeckle hyperassembly is typical for cells subjected to SG-inducing stresses. Using chemical and genetic disruption of SGs, we demonstrate that formation of microscopically visible SGs is required to trigger and maintain stress-induced paraspeckle assembly. Mechanistically, SGs may sequester negative regulators of paraspeckle formation, such as UBAP2L, alleviating their inhibitory effect on paraspeckles. Our study reveals a novel function for SGs as positive regulators of nuclear RNP granule assembly and suggests a role for disturbed SG-paraspeckle crosstalk in human disease