Oxygen free radicals play a role in cellular differentiation: An hypothesis

Evidence from a variety of sources supports the view that oxygen free radicals play a role in cellular differentiation. It is postulated that cellular differentiation is accompanied by changes in the redox state of cells. Differentiated cells have a relatively more prooxidizing or less reducing intracellular environment than the undifferentiated or dedifferentiated cells. Changes in the redox balance during differentiation appear to be due to an increase in the rate of O₂⁻ generation. Differentiated cells, in general, exhibit higher rates of cyanide-resistant respiration, cyanide-insensitive SOD activity, and peroxide concentration and lower levels of GSH as compared to undifferentiated cells. The effects of free radicals on cellular differentiation may be mediated by the consequent changes in ionic composition.     

Adaptation mechanism of the aspartate receptor: electrostatics of the adaptation subdomain play a key role in modulating kinase activity

The aspartate receptor of the Escherichia coli and Salmonella typhimurium chemotaxis pathway generates a transmembrane signal that regulates the activity of the cytoplasmic kinase CheA. Previous studies have identified a region of the cytoplasmic domain that is critical to receptor adaptation and kinase regulation. This region, termed the adaptation subdomain, contains a high density of acidic residues, including specific glutamate residues that serve as receptor adaptation sites. However, the mechanism of signal propagation through this region remains poorly understood. This study uses site-directed mutagenesis to neutralize each acidic residue within the subdomain to probe the hypothesis that electrostatics in this region play a significant role in the mechanism of kinase activation and modulation. Each point mutant was tested for its ability to regulate chemotaxis in vivo and kinase activity in vitro. Four point mutants (D273N, E281Q, D288N, and E477Q) were found to superactivate the kinase relative to the wild-type receptor, and all four of these kinase-activating substitutions are located along the same intersubunit interface as the adaptation sites. These activating substitutions retained the wild-type ability of the attractant-occupied receptor to inhibit kinase activity. When combined in a quadruple mutant (D273N/E281Q/D288N/E477Q), the four charge-neutralizing substitutions locked the receptor in a kinase-superactivating state that could not be fully inactivated by the attractant. Similar lock-on character was observed for a charge reversal substitution, D273R. Together, these results implicate the electrostatic interactions at the intersubunit interface as a major player in signal transduction and kinase regulation. The negative charge in this region destabilizes the local structure in a way that enhances conformational dynamics, as detected by disulfide trapping, and this effect is reversed by charge neutralization of the adaptation sites. Finally, two substitutions (E308Q and E463Q) preserved normal kinase activation in vitro but blocked cellular chemotaxis in vivo, suggesting that these sites lie within the docking site of an adaptation enzyme, CheR or CheB. Overall, this study highlights the importance of electrostatics in signal transduction and regulation of kinase activity by the cytoplasmic domain of the aspartate receptor.     

Fighting climate change: soil bacteria communities and topography play a role in plant colonization of desert areas

Global warming has exacerbated desertification in arid regions. Exploring the environmental variables and microbial communities that drive the dynamics of geographic patterns of desert crops is important for large-scale standardization of crops that can control desertification. Here, predictions based on future climate data from CMIP6 show that a steady expand in the suitable production areas for three desert plants (Cistanche deserticola, Cynomorium songaricum and Cistanche salsa) under global warming, demonstrating their high adaptability to future climate change. We examined the biogeography of three desert plant soil bacteria communities and assessed the environmental factors affecting the community assembly process. The α-diversity significantly decreased along elevated latitudes, indicating that the soil bacterial communities of the three species have latitude diversity patterns. The neutral community model evaluated 66.6% of the explained variance of the bacterial community in the soil of desert plants and Modified Stochasticity Ratio <0.5, suggesting that deterministic processes dominate the assembly of bacterial communities in three desert plants. Moreover, topography (longitude, elevation) and precipitation as well as key OTUs (OTU4911: Streptomyces eurythermus and OTU4672: Streptomyces flaveus) drive the colonization of three desert plants. This research offers a promising solution for desert management in arid areas under global warming.     

Carabid life-cycle strategies and climate change: a study on an altitude transect

Abstract.

• 1 There was little overlap in the species composition of carabid beetle assemblages sampled below 450 m and above 800 m on an altitude transect and the first axis of a DECORANA ordination was closely correlated with altitude (r₁₁= 0.93, P < 0.001), probably reflecting the differing temperature requirements of different species.
• 2 Life-cycle strategies of two low-altitude species, found predominantly below 600 m, and two species caught above 600 m a.s.l., have been determined, using mandible wear to identify whether the females breed in the calendar year that they emerge as adults or in the year following.
• 3 Nebria salina has an annual cycle at 630 m. Pterostichus madidus and Calathus fuscipes were both biennial at altitudes above 300 m although predominantly annual at low altitude. N.gyllenhali was biennial above 600 m and it is not known whether it is able to switch to an annual cycle at low altitude.
• 4 Both N.salina and N.gyllenhali ceased activity soon after emergence, an adaptation which preserves their mandibles from wear.
• 5 At altitudes of 305 m and 430 m, P.madidus and C.fuscipes entered the breeding season with 33% and 56% reduction in mandible tip length, possibly reducing their reproductive output.
• 6 The necessity for relatively sharp mandibles on entry into the breeding season may restrict the capacity of carabids to respond to a temperature change by switching from annual to biennial cycles, and vice versa, adding support to the suggestion that carabids are more likely to respond to climate change by shifting distributions than by physiological adaptation.

     

Hippocampal dose during Linac-based stereotactic radiotherapy for brain metastases: An observational study

IntroductionAim of the present study is to evaluate homolateral and contralateral hippocampus (H-H, C-H, respectively) dose during Fractionated Stereotactic Radiotherapy (FSRT) or Radiosurgery (SRS) for brain metastases (BM).Materials & methodsPatients with BM < 5, size ≤ 30 mm, KPS ≥ 80 and a life expectancy > 3 months, were considered for SRS/FSRT (total dose 15–30 Gy, 1–5 fractions). For each BM, a Flattening Filter Free (FFF) Volumetric Modulated Arc Therapy (VMAT) plan was generated with one or two arcs. Hippocampi were not considered during optimizations phase and were contoured and evaluated retrospectively in terms of dose: the Dmedian, Dmean, D0.1cc and the V1Gy, V2Gy, V5Gy and V10Gy were analyzed.ResultsFrom April 2014 to December 2015, 81 BM were treated with FFF-FSRT/SRS. For the H-H, the average values of Dmedian, Dmean and D0.1cc were 1.5Gy, 1.54Gy and 2.2Gy, respectively, while the V1Gy, V2Gy, V5Gy and V10Gy values were 25%, 8.9%, 8.9% and 2.1%, respectively. For the C–H, the average Dmedian, Dmean and D0.1 cc were 0.7Gy, 0.7Gy, 0.9Gy, respectively, while the average values of V1Gy, V2Gy, V5Gy and V10Gy were 18%, 10.2%, 2.8% and 1.4%, respectively. Tumor dimension, tumor cranial-caudal length and the distance between BM and H-H were correlated to Dmedian, Dmean and D0.1cc. For C-H, only the distance from PTV was correlated with a dose reduction.ConclusionDuring FFF-FSRT/SRS, hippocampus received a negligible dose. Despite its clinical significance is still under evaluation, in patients with a long life expectancy, H-H should be considered during Linac-based FSRT/SRS.     

An architectural hypothesis for direction selectivity in the visual cortex: the role of spatially asymmetric intracortical inhibition

Within a linear field approach, an architectural model for simple cell direction selectivity in the visual cortex is proposed. The origin of direction selectivity is related to recurrent intracortical interactions with a spatially asymmetric character along the axis of stimulus motion. No explicit asymmetric temporal mechanisms are introduced or adopted. The analytical investigation of network behavior, carried out under the assumption of a linear superposition of geniculate and intracortical contributions, shows that motion sensitivity of the resulting receptive fields emerges as a dynamic property of the cortical network without any feed-forward direction selectivity bias. A detailed analysis of the effects of the architectural characteristics of the cortical network on directionality and velocity-response curves was conducted by systematically varying the model's parameters. Received: 8 May 1998 / Accepted in revised form: 10 November 1998     

Part II: Fibroblasts preferentially migrate in the direction of principal strain

A growing body of evidence suggests that the sensory information from the cytoskeleton and integrins may be responsible for guiding migration during mechano- and haptotaxis. However, the dual function of these subcellular structures as mechano-sensors and -actuators is only partially understood. Using a new cell chamber described in the preceding companion paper (Ref to part I, Raeber et al. 2007a) we investigated the migration response of adhesion-dependent fibroblasts embedded 3-dimensionally within synthetic protease-sensitive poly(ethylene glycol) hydrogels to stepwise and cyclic mechanical loads. To that end, we developed a spatially and temporally resolved migration analysis technique capable of providing estimates of statistical cell migration parameters along and perpendicular to the main strain direction. Fibroblasts reoriented themselves in the direction of principal strain, increased their proteolytic migration activity and moved preferentially parallel to the principal strain axis. These results point to a possible correlation between planes of iso-strain and migration direction.     

The role of natural plant products in modulating the immune system: An adaptable approach for combating disease in grazing animals

Plants provide herbivores with an array of chemicals with the potential to improve health and well-being. For instance, phytochemicals, known as secondary compounds, which protect plants from consumers and pests can adversely affect cellular and metabolic processes in herbivores, but at low doses and in appropriate mixtures, they can have beneficial effects on animal nutrition and health, though the latter has not been explored in great breadth or depth. In this review, we summarize the potential impact of natural plant products on immunomodulation and other therapeutic effects in herbivores. Development of preventative strategies to help animals resist disease would be a more economical, ecological and socially effective long-term healthcare strategy than treating diseases. In this realm, immunomodulation promoted by forages emerges as an interesting alternative and complement to chemotherapy. The challenge for feeding systems will be to incorporate mixes of plants with bioactive properties in ways that enhance health without compromising animal production and well-being. A solution to this challenge may involve developing management programs that acknowledge the ability of animals to learn about the beneficial effects of diverse foods.     

Sleep quality in pregnancy during treatment with Bryophyllum pinnatum: An observational study

IntroductionPoor sleep quality in pregnancy is frequent. A treatment with sedatives is problematic due to possible adverse effects for mother and embryo/foetus. In the present study, we investigated the sedative effect of Bryophyllum pinnatum, a phytotherapeutic medication used in anthroposophic medicine. In previous clinical studies on its tocolytic effect, B. pinnatum showed a good risk/benefit ratio for mother and child. A recent analysis of the prescribing pattern for B. pinnatum in a network of anthroposophic physicians revealed sleep disorders as one of the most frequent diagnoses for which these preparations are prescribed.Materials and methodsIn this prospective, multi-centre, observational study, pregnant women suffering from sleep problems were treated with B. pinnatum (350 mg tablets, 50% leaf press juice, Weleda AG, Arlesheim, dosage at physician's consideration). Sleep quality, daily sleepiness and fatigue were assessed with the aid of standardised questionnaires, at the beginning of the treatment and after 2 weeks. Possible adverse drug reactions perceived by the patients during the treatment were recorded.ResultsThe number of wake-ups, as well as the subjective quality of sleep was significantly improved at the end of the treatment with B. pinnatum. The Epworth Sleeping Scale decreased, indicating a decrease of the tiredness during the day. There was, however, no evidence for prolongation of the sleep duration, reduction in the time to fall asleep, as well as change in the Fatigue Severity Scale after B. pinnatum. No serious adverse drug reactions were detected.ConclusionB. pinnatum is a suitable treatment of sleep problems in pregnancy. The data of this study encourage further clinical investigations on the use of B. pinnatum in sleep disorders.     

Evidence for a role of antagonistic cocontraction in controlling trunk stiffness during lifting

Activity of the abdominal muscles during symmetric lifting has been a consistent finding in many studies. It has been hypothesized that this antagonistic coactivation increases trunk stiffness to provide stability to the spine. To test this, we investigated whether abdominal activity in lifting is increased in response to destabilizing conditions.

Ten healthy male subjects lifted 35 l containers containing 15 l of water (unstable condition), or ice (stable condition). 3D-kinematics, ground reaction forces, and EMG of selected trunk muscles were recorded. Euler angles of the thorax relative to the pelvis were determined. Inverse dynamics was used to calculate moments about L5S1. Averaged normalized abdominal EMG activity was calculated to express coactivation and an EMG-driven trunk muscle model was used to estimate the flexor moment produced by these muscles and to estimate the L5S1 compression force.

Abdominal coactivation was significantly higher when lifting the unstable load. This coincided with significant increases in estimated moments produced by the antagonist muscles and in estimated compression forces on the L5S1 disc, except at the instant of the peak moment about L5S1. The lifting style was not affected by load instability as evidenced by the absence of effects on moments about L5S1 and angles of the thorax relative to the pelvis. The data support the interpretation of abdominal cocontraction during lifting as subserving spinal stability. An alternative function of the increased trunk stiffness due to cocontraction might be to achieve more precise control over the trajectory of lifted weight in order to avoid sloshing of the water mass in the box and the consequent perturbations.     

Breastfeeding self-efficacy of women using second-line strategies for healthy term infants in the first week postpartum: an Australian observational study

Background

Breastfeeding self-efficacy (BFSE) supports breastfeeding initiation and duration. Challenges to breastfeeding may undermine BFSE, but second-line strategies including nipple shields, syringe, cup, supply line and bottle feeding may support breastfeeding until challenges are resolved. The primary aim of this study was to examine BFSE in a sample of women using second-line strategies for feeding healthy term infants in the first week postpartum.

Methods

A retrospective self-report study was conducted using the Breastfeeding Self-Efficacy Scale - Short Form (BSES-SF), demographic and infant feeding questionnaires. Breastfeeding women who gave birth to a singleton healthy term infant at one private metropolitan birthing facility in Australia from November 2008 to February 2009 returned anonymous questionnaires by mail.

Results

A total of 128 (73 multiparous, 55 primiparous) women participated in the study. The mean BSES-SF score was 51.18 (Standard deviation, SD: 12.48). The median BSES-SF score was 53. Of women using a second-line strategy, 16 exceeded the median, and 42 were below. Analyses using Kruskal-Wallis tests confirmed this difference was statistically significant (H = 21.569, p = 0.001). The rate of second-line strategy use was 48%. The four most commonly used second-line strategies were: bottles with regular teats (77%); syringe feeding (44%); bottles with wide teats (34%); and nipple shields (27%). Seven key challenges were identified that contributed to the decision to use second-line strategies, including: nipple pain (40%); unsettled infant (40%); insufficient milk supply (37%); fatigue (37%); night nursery care (25%); infant weight loss?>?10% (24%); and maternal birth associated pain (20%). Skin-to-skin contact at birth was commonly reported (93%). At seven days postpartum 124 women (97%) were continuing to breastfeed.

Conclusions

The high rate of use of second-line strategies identified in this study and high rate of breastfeeding at day seven despite lower BFSE indicate that such practices should not be overlooked by health professionals. The design of this study does not enable determination of cause-effect relationships to identify factors which contribute to use of second-line strategies. Nevertheless, the significantly lower BSES-SF score of women using a second-line strategy highlights this group of women have particular needs that require attention.

     

A role of myocardial stiffness in cell-based cardiac repair: a hypothesis

Determining which time point is optimal for bone marrow-derived cell (BMC) transplantation for acute myocardial infarction (AMI) has attracted a great deal of attention. Studies have verified the interaction between cell treatment effect and transfer timing and have suggested that the optimal time frame for BMC therapy is day 4 to day 7 after AMI. However, the potential mechanism underlying the time-dependent therapeutic response remains unclear. Recently, a growing body of in vitro evidence has suggested that stem cells are able to feel and respond to the stiffness of their microenvironment to commit to a relevant lineage, indicating that soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Simultaneously, considering the fact that the myocardium post-infarction experiences a time-dependent stiffness change from flexible to rigid as a result of myocardial remodelling following tissue necrosis and massive extracellular matrix deposition, we presume that the myocardial stiffness within a certain time frame (possibly day 4–7) post-AMI might provide a more favourable physical microenvironment for the phenotypic plasticity and functional specification of engrafted BMCs committed to some cell lineages, such as endothelial cells, vascular smooth muscle cells or cardiomyocytes. The beneficial effect facilitates angiogenesis and myocardiogenesis in the infarcted heart, and subsequently leads to more amelioration of cardiac functions. If the present hypothesis were true, it would be of great help to understand the mechanism underlying the optimal timing for BMC transplantation and to establish a direction for the time selection of cell therapy.     

Global agricultural intensification during climate change: a role for genomics

Agriculture is now facing the ‘perfect storm’ of climate change, increasing costs of fertilizer and rising food demands from a larger and wealthier human population. These factors point to a global food deficit unless the efficiency and resilience of crop production is increased. The intensification of agriculture has focused on improving production under optimized conditions, with significant agronomic inputs. Furthermore, the intensive cultivation of a limited number of crops has drastically narrowed the number of plant species humans rely on. A new agricultural paradigm is required, reducing dependence on high inputs and increasing crop diversity, yield stability and environmental resilience. Genomics offers unprecedented opportunities to increase crop yield, quality and stability of production through advanced breeding strategies, enhancing the resilience of major crops to climate variability, and increasing the productivity and range of minor crops to diversify the food supply. Here we review the state of the art of genomic‐assisted breeding for the most important staples that feed the world, and how to use and adapt such genomic tools to accelerate development of both major and minor crops with desired traits that enhance adaptation to, or mitigate the effects of climate change.     

Evaluating drivers of vulnerability to climate change: a guide for insect conservation strategies

Ongoing global climate change presents serious challenges in conservation biology, forcing us to revisit previous tools and principles based on how species may respond to novel climatic conditions. There is currently a major gap between predictions of species vulnerability and management strategies, despite the fact that linking these areas is fundamental for future biodiversity conservation. Herein, we evaluate what drives vulnerability to climate change in three Iberian endemic water beetles, representing three independent colonizations of the same habitat, employing comparative thermal physiology, species distribution models and estimations of species dispersal capacity. We derive conservation strategies for each species based on their differential capacity to persist and/or potential to shift their ranges in response to global warming. We demonstrate that species may be affected by climatic warming in very different ways, despite having broadly similar ecological and biogeographical traits. The proposed framework provides an effective complement to traditional species vulnerability assessments, and could aid the development of more effective conservation strategies in the face of global warming.     

Resolving emotional conflict: a role for the rostral anterior cingulate cortex in modulating activity in the amygdala

Effective mental functioning requires that cognition be protected from emotional conflict due to interference by task-irrelevant emotionally salient stimuli. The neural mechanisms by which the brain detects and resolves emotional conflict are still largely unknown, however. Drawing on the classic Stroop conflict task, we developed a protocol that allowed us to dissociate the generation and monitoring of emotional conflict from its resolution. Using functional magnetic resonance imaging (fMRI), we find that activity in the amygdala and dorsomedial and dorsolateral prefrontal cortices reflects the amount of emotional conflict. By contrast, the resolution of emotional conflict is associated with activation of the rostral anterior cingulate cortex. Activation of the rostral cingulate is predicted by the amount of previous-trial conflict-related neural activity and is accompanied by a simultaneous and correlated reduction of amygdalar activity. These data suggest that emotional conflict is resolved through top-down inhibition of amygdalar activity by the rostral cingulate cortex.     

Mountain refugia play a role in soil arthropod speciation on Madagascar: a case study of the endemic giant fire-millipede genus Aphistogoniulus

To elucidate the speciation mechanisms prevalent within hotspots of biodiversity, and the evolutionary processes behind the rise of their species-rich and endemic biota, we investigated the phylogeny of the giant fire-millipede genus Aphistogoniulus Silvestri, 1897, a Malagasy endemic. This study is the first comprehensive (molecular and morphological) phylogenetic study focusing on millipede (class Diplopoda) speciation on Madagascar. The morphological analysis is based on 35 morphological characters and incorporates ten described as well as two newly described species (A. rubrodorsalisn. sp. and A. jeekelin. sp.) of Aphistogoniulus. The molecular analysis is based on both mitochondrial (COI and 16S), and nuclear genes (complete 18S rDNA), together comprised of 3031 base pairs, which were successfully sequenced for 31 individual specimens and eight species of Aphistogoniulus. In addition to the null-model (speciation by distance), two diversification models, mountain refugia and ecotone shift, were discovered to play a role in the speciation of soil arthropods on Madagascar. Mountain refugia were important in the speciation of the A. cowani clade, with three species occurring in the Andringitra and Ranomafana Mountains in the southeast (A. cowani), the Ambohijanahary and Ambohitantely Mountains in the mid-west (A. sanguineus), and the Marojejy Mountain in the northeast (A. rubrodorsalisn. sp.). An ecotone shift from the eastern rainforest to the unique subarid spiny forest of Mahavelo was discovered in the A. vampyrus-A. aridus species-pair. In the monophyletic A. diabolicus clade, evidence for divergent evolution of sexual morphology was detected: species with greatly enlarged gonopods are sister-taxa to species with normal sized gonopods. Among the large-bodied Spirobolida genera of Madagascar, Colossobolus and Sanguinobolus were found to be close sister-genera to Aphistogoniulus. Forest destruction has caused forest corridors between populations to disappear, which might limit the possible resolution of biogeographic analyses on Madagascar.