Sequential nearest-neighbor effects on computed <Superscript>13</Superscript>C<Superscript>α</Superscript> chemical shifts

To evaluate sequential nearest-neighbor effects on quantum-chemical calculations of ¹³C^α chemical shifts, we selected the structure of the nucleic acid binding (NAB) protein from the SARS coronavirus determined by NMR in solution (PDB id 2K87). NAB is a 116-residue α/β protein, which contains 9 prolines and has 50% of its residues located in loops and turns. Overall, the results presented here show that sizeable nearest-neighbor effects are seen only for residues preceding proline, where Pro introduces an overestimation, on average, of 1.73 ppm in the computed ¹³C^α chemical shifts. A new ensemble of 20 conformers representing the NMR structure of the NAB, which was calculated with an input containing backbone torsion angle constraints derived from the theoretical ¹³C^α chemical shifts as supplementary data to the NOE distance constraints, exhibits very similar topology and comparable agreement with the NOE constraints as the published NMR structure. However, the two structures differ in the patterns of differences between observed and computed ¹³C^α chemical shifts, Δ _ca,i , for the individual residues along the sequence. This indicates that the Δ _ca,i -values for the NAB protein are primarily a consequence of the limited sampling by the bundles of 20 conformers used, as in common practice, to represent the two NMR structures, rather than of local flaws in the structures.     

Anti‐atherosclerotic effects of vitamin E – myth or reality?

Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.     

Does COMT genotype influence the effects of d‐amphetamine on executive functioning?

In a widely cited study, Mattay et al. reported that amphetamine (0.25 mg/kg oral, or 17 mg for a 68 kg individual) impaired behavioral and brain indices of executive functioning, measured using the Wisconsin Card Sorting Task (WCST) and N‐Back working memory task, in 6 individuals homozygous for the met allele of the val158met polymorphism in the catechol‐O‐methyltransferase (COMT) gene, whereas it improved executive functioning in 10 individuals homozygous for the more active val allele. We attempted to replicate their behavioral findings in a larger sample, using similar executive functioning tasks and a broader range of amphetamine doses. Over four sessions, n = 200 healthy normal adults received oral placebo, d‐amphetamine 5, 10, and 20 mg (average of 0.07, 0.15 and 0.29 mg/kg), under counterbalanced double‐blind conditions and completed WCST and N‐back tests of executive functioning. Amphetamine had typical effects on blood pressure and processing speed but did not affect executive functioning. COMT genotype (val158met) was not related to executive functioning under placebo or amphetamine conditions, even when we compared only the homozygous val/val and met/met genotypes at the highest dose of amphetamine (20 mg). Thus, we were not able to replicate the behavioral interaction between COMT and amphetamine seen in Mattay et al. We discuss possible differences between the studies and the implications of our findings for the use of COMT genotyping to predict clinical responses to dopaminergic drugs, and the use of intermediate phenotypes in genetic research.     

Do consumer‐mediated negative effects on plant establishment outweigh the positive effects of a nurse plant?

Many studies demonstrated the importance of facilitative effect by nurse plant on seedling establishment. Few studies evaluated the negative effects of consumers on plant establishment under nurse plants by dealing with them during multiple demographic processes. We investigated the balance between the facilitative effect and negative effects of consumers during multiple demographic processes in Malawi in southeastern Africa. We chose Ficus natalensis as a nurse plant and compared it with three other microsites in tropical woodlands: Brachystegia floribunda (a dominant woodland species), Uapaca kirkiana (a woodland species), and a treeless site. We quantified the seed rain, postdispersal seed predation, germination, and seedling survival of Syzygium guineense ssp. afromontanum (a common forest species). Within each microsite, we quantified the overall probability of recruitment. We also measured seedling abundance of S. guineense ssp. afromontanum. We found that Ficus natalensis exerted both positive and negative impacts on the establishment of S. guineense ssp. afromontanum. Ficus natalensis facilitated seed deposition, seed germination, and seedling survival. On the other hand, seed removal at postdispersal stage was highest under F. natalensis. Interestingly, B. floribunda also had positive effects on germination and seedling survival, but not on seed deposition. When we excluded the seed arrival stage from our estimation of the recruitment probability, the highest value was found under B. floribunda, not under F. natalensis. When we included the seed arrival stage, however, the order of recruitment probability between F. natalensis and B. floribunda was reversed. The probability was one order of magnitude higher under F. natalensis than under B. floribunda. Our estimation of the probability which included the seed arrival stage was consistent with natural patterns of S. guineense ssp. afromontanum establishment. Despite the presence of opposite effects, the net effects of F. natalensis on S. guineense ssp. afromontanum recruitment in tropical woodlands can be positive.     

R-Ras regulates β<Subscript>1</Subscript>-integrin trafficking via effects on membrane ruffling and endocytosis

Background  

Integrin-mediated cell adhesion and spreading is dramatically enhanced by activation of the small GTPase, R-Ras. Moreover, R-Ras localizes to the leading edge of migrating cells, and regulates membrane protrusion. The exact mechanisms by which R-Ras regulates integrin function are not fully known. Nor is much known about the spatiotemporal relationship between these two molecules, an understanding of which may provide insight into R-Ras regulation of integrins.     

Anesthetic effects of a three-drugs mixture —comparison of administrative routes and antagonistic effects of atipamezole in mice—

The anesthetic mixture of medetomidine (MED), midazolam (MID) and butorphanol (BUT) produced anesthetic duration of around 40 minutes (min) in ICR mice. We reported that this anesthetic mixture produced almost the same anesthetic effects in both male and female BALB/c and C57BL/6J strains. Intraperitoneal (IP) administration of drugs has been widely used in mice. However, various injectable routes of the anesthetic mixture may cause different anesthetic effects. First, we examined effects of the anesthetic mixture by subcutaneous (SC) and intravenous (IV) injection compared to IP injection. After injection of the anesthetic mixture, administration of atipamezole (ATI) induced mice recovery from anesthesia. Secondly, we examined how different dosage and optimum injection timing of ATI affected mice recovery from anesthesia. We used an anesthetic score to measure anesthetic duration and a pulse oximeter to monitor vital signs under anesthesia. Usually, drugs from SC injection work more weakly than IP or IV injection. However, we found no significant differences of anesthetic duration among the three different injection routes. Antagonistic effects of ATI (0.3 mg/kg and 1.5 mg/kg) worked equally when administered at 30 min after injection of the anesthetic mixture. Antagonistic effects of ATI (1.5 mg/kg) were stronger than ATI (0.3 mg/kg) at 10 min after injection of the anesthetic mixture. The anesthetic mixture is a useful drug to induce nearly the same anesthetic effects by different injection routes and has an antagonist of ATI which helps mice quickly recover from anesthesia. These results may contribute to the welfare of laboratory animals.     

Do multitrophic interactions override N fertilization effects on <Emphasis Type="Italic">Operophtera</Emphasis> larvae?

We examined how performance of Operophtera brumata (Lepidoptera) larvae was affected by nitrogen (N) fertilization of boreal forest understorey vegetation. We monitored larval densities on Vaccinium myrtillus plants for a period of 7 years in a field experiment. Preliminary results indicated that the N effect on larval densities was weak. To examine if this was due to indirect interactions with a plant pathogen, Valdensia heterodoxa, that share the same host plant, or due to top-down effects of predation, we performed both a laboratory feeding experiment (individual level) and a bird exclusion experiment (population level) in the field. At the individual level, altered food plant quality (changes in plant concentration of carbon, N, phenolics, or condensed tannins) due to repeated infection by the pathogen had no effect on larval performance, but both survival to the adult stage and adult weight were positively affected by N fertilization. Exclusion of insectivorous birds increased the frequency of larval damage on V. myrtillus shoots, indicating higher larval densities. This effect was stronger in fertilized than in unfertilized plots, indicating higher bird predation in fertilized plots. Predation may thus explain the lack of fertilization effect on larval densities in the field experiment. Our results suggest that top-down effects are more important for larval densities than bottom-up effects, and that bird predation may play an important role in population regulation of O. brumata in boreal forests.Electronic Supplementary Material Supplementary material is available for this article at     

Can <Emphasis Type="Italic">Bradyrhizobium</Emphasis> strains inoculation reduce water deficit effects on peanuts?

Drought is one of the environmental factors that most affects peanut cultivation in semi-arid regions, resulting in economic losses to growers. However, growth promoting bacteria are able to reduce water deficit damage in some plant species. In this context, this study aimed to evaluate the interaction of Bradyrhizobium strains reducing water stress effects on peanut genotypes by antioxidant enzymes activities, leaf gas exchanges and vegetative growth, as well as to determine the taxonomic positioning of strain ESA 123. The 16S rRNA gene of ESA 123 was amplified by PCR and sequenced by dideoxy Sanger sequencing method. An experiment was performed in greenhouse with three peanut genotypes (BRS Havana, CNPA 76 AM and 2012-4), two Bradyrhizobium strains (SEMIA 6144 and ESA 123), a mineral source of N and an absolute control (without N) under two water regimes (with and without irrigation). Seeds of peanut were sown and the plants were grown until 30 days after emergence. On the 20th day, the water deficit plants group had their irrigation suspended for 10 days. At in silico analyzes, ESA 123 presented 98.97% similarity with the type strain of B. kavangense. Leaf gas exchange was affected by water deficit; as well as alteration of antioxidant activities and reduction of vegetative growth variables. However, some plants inoculated with SEMIA 6144 and ESA 123 strains presented lower reductions and increment of some evaluated variables, mainly the ones inoculated with the ESA 123 strain, Bradyrhizobium sp. from the semi-arid region of Northeast Brazil. This data suggests beneficial effects of the peanut-Bradyrhizobium interaction in a water stress condition, specially with the ESA 123 strain.     

Genome-wide linkage analysis of longitudinal phenotypes using σ<Superscript>2</Superscript><Subscript>A</Subscript> random effects (SSARs) fitted by Gibbs sampling

The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the familial aggregation and evidence for linkage to change in systolic blood pressure (SBP) over time. We used Gibbs sampling to derive sigma-squared-A-random-effects (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in subsequent genome-wide linkage analyses. Additive genetic effects (sigma2A.time) were estimated to account for approximately 9.2% of the variance in the rate of change of SBP with age, while additive genetic effects (sigma2A) were estimated to account for approximately 43.9% of the variance in SBP at the mean age. The linkage results suggested that one or more major loci regulating change in SBP over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results also suggested that one or more major loci regulating level of SBP may localize to chromosomes 3, 8, and 14. Our results support a genetic component to both SBP and change in SBP with age, and are consistent with a complex, multifactorial susceptibility to the development of hypertension. The use of SSARs derived from quantitative traits as input to a conventional linkage analysis appears to be valuable in the linkage analysis of genetically complex traits. We have now demonstrated in this paper the use of SSARs in the context of longitudinal family data.     

Different effects of SNP and GSNO on mitochondrial O<Stack><Subscript>2</Subscript><Superscript>.−</Superscript></Stack>/H<Subscript>2</Subscript>O<Subscript>2</Subscript> production

Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) differently affect mitochondrial H₂O₂ release at Complex-I. mM SNP increases while GSNO decreases the release induced by succinate alone or added on top of NAD-linked substrates. Stimulation likely depends on Nitric Oxide ( ^. NO) (released by SNP but not by GSNO) inhibiting cytochrome oxidase and mitochondrial respiration. Preincubations with SNP or high GSNO (10 mM plus DTE to increases its ^. NO release) induces an inhibition of the succinate dependent H₂O₂ production consistent with a ^. NO dependent covalent modification. However maximal inhibition of the succinate dependent H₂O₂ release is obtained in the presence of low GSNO (20–100 μM), but not with SNP. This inhibition appears independent of ^. NO release since μM GSNO does not affect mitochondrial respiration, or the H₂O₂ detection systems and its effect is very rapid. Inhibition may be partly due to an increased removal of O₂^.− since GSNO chemically competes with NBT and cytochrome C in O₂^.− detection.     

Comparison of the cardiac effects between quinazoline-based α<Subscript>1</Subscript>-adrenoceptor antagonists on occlusion–reperfusion injury

Quinazoline-based compounds such as prazosin and its congeners including doxazosin, bunazosin, and terazosin are widely used as antihypertensive agents. However, there were many clinical observations showing that using these agents may result in higher risk of cardiovascular accidents in recent years. In this study, we compared the effects of four α-adrenoceptor antagonists: prazosin, doxazosin, bunazosin, and terazosin on occlusion–reperfusion injury. Langendorff-perfused rat hearts were pretreated with these four antagonists, and then the left main coronary artery was occluded. After 30 min occlusion, the hearts were reperfused for 2 h and the infarct sizes were measured. Two of the compounds studied, prazosin and doxazosin, apparently increased infarct size, CK-MB, and LDH activities after 2 h reperfusion. In contrast, bunazosin decreased infarct size and those biochemical indicators of cellular damage compared to control hearts. Although infarct size after reperfusion was differently changed by these four α-adrenoceptor antagonists, TUNEL-positive nuclei and caspase-3 protein expressions of all the groups were not significantly different. We supposed that the different effects of these four agents on infarct size came from the difference in necrosis rather than apoptosis.     

How effective are maternal effects at having effects?

The well studied trade-off between offspring size and offspring number assumes that offspring fitness increases with increasing per-offspring investment. Where mothers differ genetically or exhibit plastic variation in reproductive effort, there can be variation in per capita investment in offspring, and via this trade-off, variation in fecundity. Variation in per capita investment will affect juvenile performance directly--a classical maternal effect--while variation in fecundity will also affect offspring performance by altering the offsprings' competitive environment. The importance of this trade-off, while a focus of evolutionary research, is not often considered in discussions about population dynamics. Here, we use a factorial experiment to determine what proportion of variation in offspring performance can be ascribed to maternal effects and what proportion to the competitive environment linked to the size-number trade-off. Our results suggest that classical maternal effects are significant, but that in our system, the competitive environment, which is linked to maternal environments by fecundity, can be a far more substantial influence.     

Herbivore grazing—or trampling? Trampling effects by a large ungulate in cold high‐latitude ecosystems

Mammalian herbivores have important top‐down effects on ecological processes and landscapes by generating vegetation changes through grazing and trampling. For free‐ranging herbivores on large landscapes, trampling is an important ecological factor. However, whereas grazing is widely studied, low‐intensity trampling is rarely studied and quantified. The cold‐adapted northern tundra reindeer (Rangifer tarandus) is a wide‐ranging keystone herbivore in large open alpine and Arctic ecosystems. Reindeer may largely subsist on different species of slow‐growing ground lichens, particularly in winter. Lichen grows in dry, snow‐poor habitats with frost. Their varying elasticity makes them suitable for studying trampling. In replicated factorial experiments, high‐resolution 3D laser scanning was used to quantify lichen volume loss from trampling by a reindeer hoof. Losses were substantial, that is, about 0.3 dm³ per imprint in dry thick lichen, but depended on type of lichen mat and humidity. Immediate trampling volume loss was about twice as high in dry, compared to humid thin (2–3 cm), lichen mats and about three times as high in dry vs. humid thick (6–8 cm) lichen mats, There was no significant difference in volume loss between 100% and 50% wetted lichen. Regained volume with time was insignificant for dry lichen, whereas 50% humid lichen regained substantial volumes, and 100% humid lichen regained almost all lost volume, and mostly within 10–20 min. Reindeer trampling may have from near none to devastating effects on exposed lichen forage. During a normal week of foraging, daily moving 5 km across dry 6‐ to 8‐cm‐thick continuous lichen mats, one adult reindeer may trample a lichen volume corresponding to about a year's supply of lichen. However, the lichen humidity appears to be an important factor for trampling loss, in addition to the extent of reindeer movement.     

Community‐level effects of herbicide‐based restoration treatments: structural benefits but at what cost?

Invasive species alter ecosystem structure, impact biodiversity, and have significant economic costs. In Oregon's Willamette Valley, invasive grasses Arrhenatherum elatius and Schedonorus arundinaceus alter the dynamics of the phenologically paired interaction between an endangered butterfly, Icaricia icarioides fenderi (Fender's blue), and its larval host plant, Lupinus oreganus (Kincaid's lupine). To test methods to restore this interaction, we established a 3‐year experiment where a post‐emergent grass‐specific herbicide, fluazifop‐p‐butyl, was applied to Fender's blue habitat. Plant community data were recorded throughout the growing season at eight paired plots for 1 year prior to treatment and 3 years during treatment. We asked whether annual application of herbicide could reduce the height of invasive grasses to levels at or beneath the height of Kincaid's lupine racemes throughout the Fender's blue flight season. We hypothesized that native forb species, which are critical nectar sources for Fender's blue, would increase in cover and frequency following the release from competitive dominance of invasive grasses. Grass‐specific herbicide reduced grass height during the flight season of Fender's blue, but with several costs. We found no change in nectar and a suppression of lupine growth in plots in response to experimental herbicide treatment. Each study site had multiple secondary invaders; the long‐term impact of these new invaders is unknown. We suggest that herbicide application results in a net negative effect in the context of Fender's blue habitat restoration. That is, the costs to primary resources for Fender's blue and the influx of secondary invaders may be as problematic as the primary invasion by non‐native grasses.     

Fear in the dark? Community‐level effects of non‐lethal predators change with light regime

The total effect of predators on prey is a combination of direct consumption, and non‐consumptive effects (NCEs), such as predator‐induced changes to prey morphology, behaviour and life history. Past research into NCEs has tended to focus on pair‐wise interactions between predators and prey, while in natural ecosystems, species exist in complex communities with several trophic levels made up of multiple autotrophic and heterotropic species. To address how predator NCEs alter the photosynthetic and heterotrophic components of communities, we exposed microbial microcosms to one of three predator treatments: live predators (full predator effect), freeze‐killed predators (NCEs only) or no predators (control), and incubated them under either 12 h:12 h light:dark conditions or continual darkness. Under 12 h:12 h light:dark conditions, NCEs‐only communities never differed from predator‐free communities, but differed from live predator communities. Under conditions of continual darkness, the structure of NCEs‐only communities differed from predator‐free controls, but not from live predator communities, suggesting NCEs can be strong enough to structure communities. Predation threat may cause certain prey to induce defences, such as reductions in movement, which make them less competitive in a community setting. This reduction in competitive ability could lead to these species being driven to extinction through interspecific competition, resulting in similar communities to those in which live predators are present. Heterotrophic species whose rates of resource acquisition depend on movement rates may be affected to a greater extent than autotrophs by predator‐induced reductions in movement, accounting for our observed differences in predator NCEs in ‘dark’ and ‘light’ communities. Our results suggest that the community‐level consequences of fear are greater in the dark. Synthesis Predators affect prey through consumptive and non‐consumptive effects (NCEs) such as alterations to prey behaviour, morphology, and life history. However, predators and prey do not exist in isolated pairs, but in complex communities where they interact with many other species. Using a long term study (>10 predator generations), we show that predator NCEs alone can alter community structure under conditions of darkness, but not in a 12h:12h light:dark cycle. Our results demonstrate for the first time that although the community‐level consequences of predator NCEs may be dramatic, they depend upon the abiotic conditions of the ecosystem.     

Antimicrobial effects of α-defensins from leukocytes of the hamadryas baboon <Emphasis Type="Italic">Papio hamadryas</Emphasis>

To understand the emergence and evolutionary selection of the efficient mechanisms of innate immunity it is necessary to accumulate knowledge about the structural and functional properties of antimicrobial peptides in different animal species. The cationic antimicrobial peptides, α-defensins, were isolated from leukocytic extracts of the lower narrow-nosed monkey, hamadryas baboon Papio hamadryas, using ultrafiltration, preparative electrophoresis and reverse-phase highperformance liquid chromatography. Analysis of the antimicrobial properties of α-defensins showed that they display a wide spectrum of antimicrobial activity, comparable with that of human α-defensin HNP1, and exert bactericidal and fungicidal effects at micromolar concentrations. A study of the influence of different medium conditions on antimicrobial activity of α-defensins revealed that a higher ionic strength or the presence of blood serum leads to a marked decrease in antimicrobial activity of α-defensins, while pH has no appreciable effect on it. We found that hamadryas baboon α-defensins are able to increase the permeability of the outer and inner membranes of E. coli, suggests that the bacterial membrane is one of the major targets of the antimicrobial effects of these peptides. The revealed differences in antimicrobial activity of α-defensins may result from their structural heterogeneity, which reflects different pathways of evolution of α-defensins in primates and underlies the selectivity of their antimicrobial effect.     

Antitumor therapeutic effects of a genetically engineered <Emphasis Type="Italic">Salmonella typhimurium</Emphasis> harboring TNF-α in mice

Although the use of TNF-α in the treatment of cancer is restricted due to its non-specific cytotoxicity and narrow range of applications to different cancers in clinical trials, we investigated a safe anti-cancer drug by the use of engineered bacterial capsule harboring TNF-α. The engineered bacterial capsule was designed to target cancer cells, promote a tumor-suppressive environment, and increase the efficacy of existing cancer treatments, including chemotherapy, radiotherapy, and cell therapy. The engineered bacterial capsule was constructed with Salmonella capsulizing TNF-α protein, which was produced and capsulized by Salmonella to reduce side effects of the protein. This bacterial capsule induced a tumor-suppressive environment through the activation of natural killer cells. Engineered bacterial capsule invaded tumor cells, released TNF-α, and induced apoptosis of tumor cells without apparent side effects. In a murine melanoma model, the bacterial capsule of TNF-α significantly inhibited tumor growth by 80–100% and prolonged the survival of the mice. When tested in combination with chemotherapy (cisplatin), antibiotics, and vaccine, recombinant microbial treatment increased the anti-tumor effects of existing therapies. The anti-tumor effects of the bacterial capsule of TNF-α were also observed in cervical cancer, melanoma, breast cancer, colon cancer, and renal carcinoma. These results suggest that the bacterial capsule of TNF-α is a promising strategy for TNF-α treatment.     

Internal exposure to neutron-activated <Superscript>56</Superscript>Mn dioxide powder in Wistar rats—Part 2: pathological effects

To fully understand the radiation effects of the atomic bombing of Hiroshima and Nagasaki among the survivors, radiation from neutron-induced radioisotopes in soil and other materials should be considered in addition to the initial radiation directly received from the bombs. This might be important for evaluating the radiation risks to the people who moved to these cities soon after the detonations and probably inhaled activated radioactive “dust.” Manganese-56 is known to be one of the dominant radioisotopes produced in soil by neutrons. Due to its short physical half-life, ⁵⁶Mn emits residual radiation during the first hours after explosion. Hence, the biological effects of internal exposure of Wistar rats to ⁵⁶Mn were investigated in the present study. MnO₂ powder was activated by a neutron beam to produce radioactive ⁵⁶Mn. Rats were divided into four groups: those exposed to ⁵⁶Mn, to non-radioactive Mn, to ⁶⁰Co γ rays (2 Gy, whole body), and those not exposed to any additional radiation (control). On days 3, 14, and 60 after exposure, the animals were killed and major organs were dissected and subjected to histopathological analysis. As described in more detail by an accompanying publication, the highest internal radiation dose was observed in the digestive system of the rats, followed by the lungs. It was found that the number of mitotic cells increased in the small intestine on day 3 after ⁵⁶Mn and ⁶⁰Co exposure, and this change persisted only in ⁵⁶Mn-exposed animals. Lung tissue was severely damaged only by exposure to ⁵⁶Mn, despite a rather low radiation dose (less than 0.1 Gy). These data suggest that internal exposure to ⁵⁶Mn has a significant biological impact on the lungs and small intestine.     

The effects of short-term uniaxial strain on the mechanical properties of mesenchymal stem cells upon TGF-β<Subscript>1</Subscript> stimulation

Cellular mechanical characteristics represent cell ability to produce tissue-specific metabolites. Therefore, to achieve effective cell therapy, a better understanding of the effects of chemo-mechanical stimuli on the mechanical properties of in vitro-treated cells is essential. Herein, we investigated the effects of uniaxial strain on the mechanical properties of mesenchymal stem cells (MSCs) upon transforming growth factor beta 1 (TGF-β₁) stimulation. The MSCs were categorized into control and test groups. In one test group, the MSCs were treated by TGF-β₁ for 6 d, and in the other, they were additionally subjected to 1-d uniaxial strain on day 2. The cell mechanical properties and smooth muscle (SM) gene expression were assessed on days 2, 4, and 6. During the entire experiment, the MSCs treated by TGF-β₁ ± uniaxial strain were induced to differentiate into SM-like cells by significantly upregulation of α-actin, SM22α, and h1-calponin in respect to the control samples. When the MSCs were treated with TGF-β₁ alone, their stiffness and viscosity decreased significantly on day 2 and then increased by increase in culture time. When the cells were subjected to 1-d uniaxial strain upon TGF-β₁ stimulation, their stiffness and viscosity significantly increased on days 2 and 4 and then decreased on day 6 to a level comparable to that of TGF-β₁ group. Different paths were noticeable among the treated samples to reach nearly similar states on day 6. It seems that uniaxial strain activates mechanobiological cascades by which cellular mechanical behavior can be regulated after its removal. However, these effects are transient and would diminish over time. The findings may be helpful in the chemo-mechanical regulation of MSCs.