Computational exploration of treadmilling and protrusion growth observed in fire ant rafts

Collective living systems regularly achieve cooperative emergent functions that individual organisms could not accomplish alone. The rafts of fire ants (Solenopsis invicta) are often studied in this context for their ability to create aggregated structures comprised entirely of their own bodies, including tether-like protrusions that facilitate exploration of and escape from flooded environments. While similar protrusions are observed in cytoskeletons and cel- lular aggregates, they are generally dependent on morphogens or external gradients leaving the isolated role of local interactions poorly understood. Here we demonstrate through an ant-inspired, agent-based numerical model how protrusions in ant rafts may emerge sponta- neously due to local interactions. The model is comprised of a condensed structural network of agents that represents the monolayer of interconnected worker ants, which floats on the water and gives ant rafts their form. Experimentally, this layer perpetually contracts, which we capture through the pairwise contraction of all neighboring structural agents at a strain rate of&nbsp;d_&nbsp;. On top of the structural layer, we model a dispersed, on-lattice layer of motile agents that represents free ants, which walk on top of the floating network. Experimentally, these self-propelled free ants walk with some mean persistence length and speed that we capture through an ant-inspired phenomenological model. Local interactions occur between neighboring free ants within some radius of detection,&nbsp;R, and the persistence length of freely active agents is tuned through a noise parameter,&nbsp;&eta;&nbsp;as introduced by the Vicsek model. Both&nbsp;R&nbsp;and&nbsp;&eta;&nbsp;where fixed to match the experimental trajectories of free ants. Treadmilling of the raft occurs as agents transition between the structural and free layers in accordance with experimental observations. Ultimately, we demonstrate how phases of exploratory pro- trusion growth may be induced by increased ant activity as characterized by a dimension- less parameter,&nbsp;A. These results provide an example in which functional morphogenesis of a living system may emerge purely from local interactions at the constituent length scale, thereby providing a source of inspiration for the development of decentralized, autonomous active matter and swarm robotics. </div

Continuous cultivation of photosynthetic microorganisms: approaches, applications and future trends

The possibility of using photosynthetic microorganisms, such as cyanobacteria and microalgae, for converting light and carbon dioxide into valuable biochemical products has raised the need for new cost-efficient processes ensuring a constant product quality. Food, feed, biofuels, cosmetics and pharmaceutics are among the sectors that can profit from the application of photosynthetic microorganisms. Biomass growth in a photobioreactor is a complex process influenced by multiple parameters, such as photosynthetic light capture and attenuation, nutrient uptake, photobioreactor hydrodynamics and gas-liquid mass transfer. In order to optimize productivity while keeping a standard product quality, a permanent control of the main cultivation parameters is necessary, where the continuous cultivation has shown to be the best option. However it is of utmost importance to recognize the singularity of continuous cultivation of cyanobacteria and microalgae due to their dependence on light availability and intensity. In this sense, this review provides comprehensive information on recent breakthroughs and possible future trends regarding technological and process improvements in continuous cultivation systems of microalgae and cyanobacteria, that will directly affect cost-effectiveness and product quality standardization. An overview of the various applications, techniques and equipment (with special emphasis on photobioreactors) in continuous cultivation of microalgae and cyanobacteria are presented. Additionally, mathematical modelling, feasibility, economics as well as the applicability of continuous cultivation into large-scale operation, are discussed.This research work was supported by the grant SFRH/BPD/98694/2013 (Bruno Fernandes) from Fundacao para a Ciencia e a Tecnologia (Portugal). The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013. The authors also thank the Project "BioInd Biotechnology and Bioengineering for improved Industrial and Agro-Food processes, REF. NORTE-07-0124-FEDER-000028" Co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDE

Fluropyrimidine single agent or doublet chemotherapy as second line treatment in advanced biliary tract cancer

Fluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P =.65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum- and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P =.68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting

Reelin Controls Progenitor Cell Migration in the Healthy and Pathological Adult Mouse Brain

Understanding the signals that control migration of neural progenitor cells in the adult brain may provide new therapeutic opportunities. Reelin is best known for its role in regulating cell migration during brain development, but we now demonstrate a novel function for reelin in the injured adult brain. First, we show that Reelin is upregulated around lesions. Second, experimentally increasing Reelin expression levels in healthy mouse brain leads to a change in the migratory behavior of subventricular zone-derived progenitors, triggering them to leave the rostral migratory stream (RMS) to which they are normally restricted during their migration to the olfactory bulb. Third, we reveal that Reelin increases endogenous progenitor cell dispersal in periventricular structures independently of any chemoattraction but via cell detachment and chemokinetic action, and thereby potentiates spontaneous cell recruitment to demyelination lesions in the corpus callosum. Conversely, animals lacking Reelin signaling exhibit reduced endogenous progenitor recruitment at the lesion site. Altogether, these results demonstrate that beyond its known role during brain development, Reelin is a key player in post-lesional cell migration in the adult brain. Finally our findings provide proof of concept that allowing progenitors to escape from the RMS is a potential therapeutic approach to promote myelin repair

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma

PURPOSE: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS: All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS: IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P &lt; .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). CONCLUSION:Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.</p

Individual participant data network meta-analysis of neoadjuvant chemotherapy or chemoradiotherapy in esophageal or gastroesophageal junction carcinoma

PURPOSEThe optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups.PATIENTS AND METHODSAll, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158).RESULTSIPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively).CONCLUSIONNeoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.Cellular mechanisms in basic and clinical gastroenterology and hepatolog