Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes

Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease. The distinct tumor microbiome from pancreatic cancer long-term survivors can be used to predict PDAC survival in humans, and transfer of long-term survivor gut microbiomes can alter the tumor microbiome and tumor growth in mouse models

Ileal immune tonus is a prognosis marker of proximal colon cancer in mice and patients

Ileal epithelial cell apoptosis and the local microbiota modulate the effects of oxaliplatin against proximal colon cancer by modulating tumor immunosurveillance. Here, we identified an ileal immune profile associated with the prognosis of colon cancer and responses to chemotherapy. The whole immune ileal transcriptome was upregulated in poor-prognosis patients with proximal colon cancer, while the colonic immunity of healthy and neoplastic areas was downregulated (except for the Th17 fingerprint) in such patients. Similar observations were made across experimental models of implanted and spontaneous murine colon cancer, showing a relationship between carcinogenesis and ileal inflammation. Conversely, oxaliplatin-based chemotherapy could restore a favorable, attenuated ileal immune fingerprint in responders. These results suggest that chemotherapy inversely shapes the immune profile of the ileum-tumor axis, influencing clinical outcome

Influence of the Escherichia coli oxyR gene function on λ prophage maintenance

In Escherichia coli hosts, hydrogen peroxide is one of the factors that may cause induction of λ prophage. Here, we demonstrate that H2O2-mediated λ prophage induction is significantly enhanced in the oxyR mutant host. The mRNA levels for cI gene expression were increased in a λ lysogen in the presence of H2O2. On the other hand, stimulation of the pM promoter by cI857 overproduced from a multicopy plasmid was decreased in the ΔoxyR mutant in the presence of H2O2 but not under normal growth conditions. The purified OxyR protein did bind specifically to the pM promoter region. This binding impaired efficiency of interaction of the cI protein with the OR3 site, while stimulating such a binding to OR2 and OR1 sites, in the regulatory region of the pM promoter. We propose that changes in cI gene expression, perhaps in combination with moderately induced SOS response, may be responsible for enhanced λ prophage induction by hydrogen peroxide in the oxyR mutant. Therefore, OxyR seems to be a factor stimulating λ prophage maintenance under conditions of oxidative stress. This proposal is discussed in the light of efficiency of induction of lambdoid prophages bearing genes coding for Shiga toxins

Methodic aspects of determining durations, disturbance size, and their impact on milking quality in pipeline milking machine

Określono zakłócenia w rurociągu mlecznym przez pomiar podciśnienia: za aparatem udojowym, różnicy ciśnień między rurociągiem podciśnienia i mlecznym, w kolektorze, w komorze podstrzykowej. Następnie dla wyżej wymienionych punktów pomiarowych przedstawiono sposoby wyznaczania: maksymalnego spadku podciśnienia, powierzchnię pod zarejestrowanym spadkiem podciśnienia i całkowitą powierzchnię w przypadku wystąpienia przeregulowania (względem podciśnienia ustalonego) przez regulator - tzw. uchyb przejściowy oraz czas trwania zakłócenia.The research allowed to determine disturbances in milk pipeline by vacuum (negative pressure) measurement: after milking apparatus, differential pressure between vacuum and milk pipeline, in collector, in chamber under teats. Then, for the above-mentioned measurement points, the work presents methods allowing to determine the following: maximum negative pressure drop, area under recorded negative pressure drop, and total area in case of readjustment (with regard to preset negative pressure value) by control unit - the so-called temporary deviation and disturbance duration

Analysis of the impact of disturbances on selected milking parameters in a pipeline milking machine

Analizowano zmiany średniego podciśnienia P14 oraz jego wahania aP14 w rurociągu mlecznym, w dojarce przewodowej przy pracy sześciu aparatów udojowych, podłączanych do instalacji kolejno i średnie podciśnienie ssania pss w aparacie udojowym po wpuszczeniu zakłócenia (10 l normalnego powietrza, 10 l normalnego powietrza sprężonego do 2 at., 20 l normalnego powietrza sprężonego do 3,5 at.) do rurociągu mlecznego. Wykazano istotny wpływ wielkości amplitudy i kształtu zakłócenia oraz całkowitego zadanego strumienia cieczy z aparatów udojowych Qmr w pierwszym cyklu pulsacji po wprowadzeniu zakłócenia (powietrza) do rurociągu mlecznego i w trzech następnych cyklach pulsacji po wprowadzeniu ww. zakłócenia na spadek podciśnienia P14 oraz na jego amplitudę wahań aP14 w strefie pracujących aparatów (w rurociągu mlecznym). Średnie podciśnienie ssania pss w aparacie udojowym jest również istotnie zależne od ww. warunków.The research involved the analysis of changes in average negative pressure P14 and its fluctuations aP14 in a milk pipeline of a milking machine during work of six milking apparatuses (each of them was connected to the installation in turn). The other analysed parameter was average negative pressure of suction pss in milking apparatus after letting a disturbance into the milk pipeline (10 l of normal air, 10 l of normal air compressed to 2 atm, 20 l of normal air compressed to 3.5 atm). The research has proven considerable impact of amplitude size and disturbance shape and total preset stream of liquid from milking apparatuses Qmr during the first pulsation cycle after letting the disturbance (air) into the milk pipeline and during the next three pulsation cycles after letting in the abovementioned disturbance on the drop of negative pressure P14 and on its fluctuation amplitude aP14 in the zone of working apparatuses (in a milk pipeline). Average negative pressure of suction pss in a milking apparatus is also significantly dependent on the above-mentioned conditions

Analysis of the influence of milk line load on milk line filling in pipeline milking machine

Analizowano stopień wypełnienia rurociągu mlecznego dojarki przewodowej w konfiguracji rurociągu mlecznego odnoga i odnoga z rurociągiem wspomagającym mycie, przy różnym jego obciążeniu cieczą. W badaniach stosowano dwa sposoby podłączania sześciu aparatów udojowych do instalacji dojarki uwzględniające kolejność podłączania aparatów a to: rozpoczynając podłączanie aparatów udojowych raz od pierwszego kurka stanowiskowego (znajdującego się najbliżej jednostki końcowej) drugim razem zaczynając podłączanie od najdalszego kurka stanowiskowego względem jednostki końcowej. Wykazano istotny wpływ całkowitego strumienia przepływu cieczy w rurociągu mlecznym Qmr, średniej prędkości tej cieczy vcrś i konfiguracji rurociągu mlecznego na stopień wypełnienia rurociągu mlecznego w. Przy pełnym obciążeniu instalacji udojowej, przy pracy sześciu aparatów udojowych o maksymalnym zadanym strumieniu wypływu cieczy z aparatu Qm = 81 min-1, zmiana stopnia wypełnienia w wynosiła, około 0,4, co wskazuje na 40% wypełnienie rurociągu mlecznego.Changes of vacuum drop and vacuum ranges in milk line of pipeline milking machine were analyzed. Two methods of connecting the six clusters to the installation were applied: first starting from the tap close to final unit and second from the tap at the largest distance from final unit. There were also taken into consideration two configurations of milk line: arm and arm with wash supporting line and three systems of vacuum control. A significant effect of total liquid stream from clusters Qmr, average velocity of liquid vcrś and configuration of milk line on filling the transport milk line was described. Filling the transport milk line of installation for configuration of arm was of 35% and for configuration of arm with wash supporting line of 40%