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Biology subjects

Ihalainen, J. A.

Publications and source records attributed to Ihalainen, J. A..

4 recordsLinked to original sources

Loss of ovarian hormones modulates the nucleic acid content of circulating extracellular vesicles and skeletal muscle metabolism in response to acute exercise

Loss of ovarian hormones (i.e., menopause) leads to negative effects on metabolic health. While exercise offers significant benefits, it seems to be insufficient to completely reverse these changes. The mechanisms by which exercise conveys the effects throughout the body are still poorly understood. Extracellular vesicles (EVs) are released into circulation during exercise. EVs carry small non-coding RNAs (sRNAs), such as microRNAs (miRs), which are proposed as mediators of the effects of exercise. We have previously shown that the miR response to acute exercise of EVs and HDL is diminished in postmenopausal women with low estrogen levels, which we were able to replicate here also in a rat model. In this study, we examined the effect of loss of ovarian hormones and acute exercise in the sRNA cargo of EV and HDL particles in female rats. We show for the first time that loss of ovarian hormones affects specifically the nucleic acid cargo of circulating EVs. We further show that the estrogen responsive miRs regulate anaerobic glycolytic pathway in skeletal muscle. Finally, we demonstrate that the loss of ovarian hormones leads to higher anaerobic energy production during an acute bout of exercise, implicating an inferior ability to sustain aerobic energy production during exercise.

physiology↗

NIRis: A low-cost, versatile imaging system for NIR fluorescence detection of phototrophic cell colonies used in science and education

A variety of costly research-grade imaging devices are available for the detection of spectroscopic features. Here we present an affordable, open-source and versatile device, suitable for a range of applications. We provide the files to print the imaging chamber with commonly available 3D printers and instructions to assemble it with easily available hardware. The imager is suitable for rapid sample screening in research, as well as for educational purposes. We provide details and results for an already proven set-up which suits the needs of a research group and students interested in UV-induced near-infrared fluorescence detection of microbial colonies grown on Petri dishes. The fluorescence signal confirms the presence of bacteriochlorophyll a in aerobic anoxygenic phototrophic bacteria (AAPB). The imager allows for the rapid detection and subsequent isolation of AAPB colonies on Petri dishes with diverse environmental samples. To this date, 15 devices have been build and more than 7000 Petri dishes have been analyzed for AAPB, leading to over 1000 new AAPB isolates. Parts can be modified depending on needs and budget. The latest version with automated switches and double band pass filters costs around 350{euro} in materials and resolves bacterial colonies with diameters of 0.5 mm and larger. The low cost and modular build allow for the integration in high school classes to educate students on light properties, fluorescence and microbiology. Computer-aided design of 3D-printed parts and programming of the employed Raspberry Pi computer could be incorporated in computer sciences classes. Students have been also inspired to do agar art with microbes. The device is currently used in seven different high schools in Finland. Additionally, a science education network of Finnish universities has incorporated it in its program for high school students. Video guides have been produced to facilitate easy operation and accessibility of the device. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/543100v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@6dfcb7org.highwire.dtl.DTLVardef@ea7fbcorg.highwire.dtl.DTLVardef@1681e78org.highwire.dtl.DTLVardef@a88d51_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Illuminating a Phytochrome Paradigm - a Light-Activated Phosphatase in Two-Component Signaling Uncovered

Bacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome from Deinococcus radiodurans (DrBphP) lacks detectable kinase activity. Here, we resolve this long-standing conundrum by comparatively analyzing the interactions and output activities of DrBphP and a bacteriophytochrome from Agrobacterium fabrum (AgP1). Whereas AgP1 acts as a conventional histidine kinase, we identify DrBphP as a light-sensitive phosphatase. While AgP1 binds its cognate response regulator only transiently, DrBphP does so strongly, which is rationalized at the structural level. Our data pinpoint two key residues affecting the balance between kinase and phosphatase activities, which immediately bears on photoreception and two-component signaling. The opposing output activities in two highly similar bacteriophytochromes inform the use of light-controllable histidine kinases and phosphatases for optogenetics.

biochemistry↗

Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release

Doxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA-carriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. These features have been largely ignored in experimenting with DNA nanostructures, but are probably the major sources of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA-carriers.

biochemistry↗