Quirky n-words in Polish: NPIs, Negative Qantifiers or neither?

The present paper investigates the contexts in which the so-called n-words - the items which are taken to be Negative Polarity Items in Slavic languages - unexpectedly occur without a licensing negation marker on the verb. This particular usage of n-words seems to point towards an ambiguous behaviour of the items in question: in an antimorphic contexts they are NPIs; otherwise they are negative quantifiers with negation having narrow scope w.r.t. the event variable. The paper tries to answer the question why the latter use is restricted to certain adverbials. I argue that the availability of 'logophoric' n-words turns on the issue of what the adverbial PP is predicated of. This intuition is formalized using Higginbothamistic view on l-(exical) syntax, where the nature of $\Theta$-identification of the adverbial with the verb is of fundamental importance. The semantic requirement, however, turns out to be insufficient. Hence the syntactic position of the PP on the hierarchy of thematic roles also has to be taken into consideration. The data analysed include adverbials of manner, reason, time, place, direction, resultatives and depictives

The Potential Role of Metalloproteinases in Neurogenesis in the Gerbil Hippocampus Following Global Forebrain Ischemia

BACKGROUND: Matrix metalloproteinases (MMPs) have recently been considered to be involved in the neurogenic response of adult neural stem/progenitor cells. However, there is a lack of information showing direct association between the activation of MMPs and the development of neuronal progenitor cells involving proliferation and/or further differentiation in vulnerable (Cornus Ammoni-CA1) and resistant (dentate gyrus-DG) to ischemic injury areas of the brain hippocampus. PRINCIPAL FINDINGS: We showed that dynamics of MMPs activation in the dentate gyrus correlated closely with the rate of proliferation and differentiation of progenitor cells into mature neurons. In contrast, in the damaged CA1 pyramidal cells layer, despite the fact that some proliferating cells exhibited antigen specific characteristic of newborn neuronal cells, these did not attain maturity. This coincides with the low, near control-level, activity of MMPs. The above results are supported by our in vitro study showing that MMP inhibitors interfered with both the proliferation and differentiation of the human neural stem cell line derived from umbilical cord blood (HUCB-NSCs) toward the neuronal lineage. CONCLUSION: Taken together, the spatial and temporal profiles of MMPs activity suggest that these proteinases could be an important component in neurogenesis-associated processes in post-ischemic brain hippocampus

Quirky n-words in Polish. NPIs, negative quantifiers or neither?

The present paper investigates the contexts in which the so-called n-words - the items which are taken to be Negative Polarity Items in Slavic languages - unexpectedly occur without a licensing negation marker on the verb. This particular usage of n-words seems to point towards an ambiguous behaviour of the items in question: in an antimorphic contexts they are NPIs; otherwise they are negative quantifiers with negation having narrow scope w.r.t. the event variable. The paper tries to answer the question why the latter use is restricted to certain adverbials. I argue that the availability of 'logophoric' n-words turns on the issue of what the adverbial PP is predicated of. This intuition is formalized using Higginbothamistic view on l-(exical) syntax, where the nature of $Theta$-identification of the adverbial with the verb is of fundamental importance. The semantic requirement, however, turns out to be insufficient. Hence the syntactic position of the PP on the hierarchy of thematic roles also has to be taken into consideration. The data analysed include adverbials of manner, reason, time, place, direction, resultatives and depictives

Elevated Plasma Concentration of 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) Highlights Malignancy of Renal Cell Carcinoma

Nicotinamide (NA) derivatives play crucial roles in various biological processes, such as inflammation, regulation of the cell cycle, and DNA repair. Recently, we proposed that 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR), an unusual derivative of NA, could be classified as an oncometabolite in bladder, breast, and lung cancer. In this study, we investigated the relations between NA metabolism and the progression, recurrence, metastasis, and survival of patients diagnosed with different histological subtypes of renal cell carcinoma (RCC). We identified alterations in plasma NA metabolism, particularly in the clear cell RCC (ccRCC) subtype, compared to papillary RCC, chromophobe RCC, and oncocytoma. Patients with ccRCC also exhibited larger tumor sizes and elevated levels of diagnostic serum biomarkers, such as hsCRP concentration and ALP activity, which were positively correlated with the plasma 4PYR. Notably, 4PYR levels were elevated in advanced stages of ccRCC cancer and were associated with a highly aggressive phenotype of ccRCC. Additionally, elevated concentrations of 4PYR were related to a higher likelihood of mortality, recurrence, and particularly metastasis in ccRCC. These findings are consistent with other studies, suggesting that NA metabolism is accelerated in RCC, leading to abnormal concentrations of 4PYR. This supports the concept of 4PYR as an oncometabolite and a potential prognostic factor in the ccRCC subtype

The new insight into extracellular NAD+NAD^{+} degradation : the contribution of CD38 and CD73 in calcific aortic valve disease

Nicotinamide adenine dinucleotide (NAD(+)) is crucial for cell energy metabolism and many signalling processes. Recently, we proved the role of ecto‐enzymes in controlling adenine nucleotide–dependent pathways during calcific aortic valve disease (CAVD). This study aimed to investigate extracellular hydrolysis of NAD(+) and mononucleotide nicotinamide (NMN) in aortic valves and aorta fragments of CAVD patients and on the inner aortic surface of ecto‐5′‐nucleotidase knockout mice (CD73−/−). Human non‐stenotic valves (n = 10) actively converted NAD(+) and NMN via both CD73 and NAD(+)‐glycohydrolase (CD38) according to our analysis with RP‐HPLC and immunofluorescence. In stenotic valves (n = 50), due to reduced CD73 activity, NAD(+) was degraded predominantly by CD38 and additionally by ALP and eNPP1. CAVD patients had significantly higher hydrolytic rates of NAD(+) (0.81 ± 0.07 vs 0.56 ± 0.10) and NMN (1.12 ± 0.10 vs 0.71 ± 0.08 nmol/min/cm(2)) compared with controls. CD38 was also primarily engaged in human vascular NAD(+) metabolism. Studies using specific ecto‐enzyme inhibitors and CD73−/− mice confirmed that CD73 is not the only enzyme involved in NAD(+) and NMN hydrolysis and that CD38 had a significant contribution to these pathways. Modifications of extracellular NAD(+) and NMN metabolism in aortic valve cells may be particularly important in valve pathology and could be a potential therapeutic target

Differences in Extracellular NAD⁺ and NMN Metabolism on the Surface of Vascular Endothelial Cells

The disruption of the metabolism of extracellular NAD+ and NMN may affect related signaling cascades and pathologies, such as cardiovascular or respiratory system diseases. We aimed to study NAD+ and NMN hydrolysis on surface endothelial cells of diverse origins and with genetically modified nucleotide catabolism pathways. We tested lung endothelial cells isolated from C57BL/6 J wild-type (WT) and C57BL/6 J CD73 knockout (CD73 KO) mice, the transfected porcine iliac artery endothelial cell line (PIEC) with the human E5NT gene for CD73 (PIEC CD73), and a mock-transfected control (PIEC MOCK), as well as HMEC-1 and H5V cells. Substrate conversion into the product was followed by high-performance liquid chromatography (HPLC). We showed profound differences in extracellular NAD+ and NMN metabolism related to the vessel origin, species diversity, and type of culture. We also confirmed the involvement of CD38 and CD73 in NAD+ and NMN cleavage

One Anastomosis Gastric Bypass Reconstitutes the Appropriate Profile of Serum Amino Acids in Patients with Morbid Obesity

Bariatric surgery leads to metabolic benefits in patients with obesity, but their mechanisms are not well understood. The appropriate composition of serum amino acids (AA) is important for sufficient supply of these components into various tissues and organs. Obesity leads to alterations in serum AA concentrations. The aim of this study was to examine the effect of one anastomosis gastric bypass (OAGB), a promising type of bariatric surgery, on serum AA concentrations, which were assayed by LC-MS in serum of 46 bariatric patients prior to and 6–9 months after OAGB, as well as in 30 lean control subjects. The results were analyzed by principle components analysis and metabolic pathway analysis. PCA analysis showed that OAGB led to normalization of serum AA concentrations of patients with obesity to a pattern similar to the control subjects, and the concentrations of essential AA remained decreased after OAGB. Changes of individual AA and their associated metabolic pathways were also presented. OAGB caused normalization of the AA profile, which may contribute to improvement of glucose homeostasis and reduction of cardiovascular risk. Considering decreased essential AA concentrations after OAGB, increased intake of high protein food should be recommended to the patients after this type of bariatric surgery

Macrophage-Derived Adenosine Deaminase 2 Correlates with M2 Macrophage Phenotype in Triple Negative Breast Cancer

Several lines of evidence suggest that altered adenosine deaminase (ADA) activity, especially its ADA2 iso-enzyme, is associated with malignant breast cancer (BC) development. Triple-negative breast cancer (TNBC) is currently the most challenging BC subtype due to its metastatic potential and recurrence. Herein, we analyzed the sources of ADA iso-enzymes in TNBC by investigating the effects of cell-to-cell interactions between TNBC cells, macrophages, lymphocytes, and endothelial cells. We also examined the potential relationship between ADA activity and cancer progression in TNBC patients. In vitro analyses demonstrated that the interactions of immune and endothelial cells with MDA-MB-231 triple negative BC cells modulated their extracellular adenosine metabolism pattern. However, they caused an increase in the ADA1 activity, and did not alter ADA2 activity in cancer cells. In turn, the co-culture of MDA-MB-231 cells with THP-1 monocyte/macrophages, Jurkat cells, and human lung microvascular endothelial cells (HULEC) caused the increase in ADA2 activity on THP-1 cells and ADA1 activity on Jurkat cells and HULEC. Clinical sample analysis revealed that TNBC patients had higher plasma ADA2 activities and lower ADA1/ADA2 ratio at advanced stages of cancer development than in the initial stages, while patients with hormone receptor positive, HER2 negative (HR+HER2-), and triple positive (HR+HER2+) breast cancers at the same stages showed opposite trends. TNBC patients also demonstrated positive associations between plasma ADA2 activity and pro-tumor M2 macrophage markers, as well as between ADA1 activity and endothelial dysfunction or inflammatory parameters. The analysis of TNBC patients, at 6 and 12 months following cancer treatment, did not showed significant changes in plasma ADA activities and macrophage polarization markers, which may be the cause of their therapeutic failure. We conclude that alterations in both ADA iso-enzymes can play a role in breast cancer development and progression by the modulation of extracellular adenosine-dependent pathways. Additionally, the changes in ADA2 activity that may contribute to the differentiation of macrophages into unfavorable pro-tumor M2 phenotype deserve special attention in TNBC