A drop of water deposited on a cold plate freezes into an ice drop with a pointy tip. While this phenomenon clearly finds its origin in the expansion of water upon freezing, a quantitative ...description of the tip singularity has remained elusive. Here we demonstrate how the geometry of the freezing front, determined by heat transfer considerations, is crucial for the tip formation. We perform systematic measurements of the angles of the conical tip, and reveal the dynamics of the solidification front in a Hele-Shaw geometry. It is found that the cone angle is independent of substrate temperature and wetting angle, suggesting a universal, self-similar mechanism that does not depend on the rate of solidification. We propose a model for the freezing front and derive resulting tip angles analytically, in good agreement with the experiments.
Symbiotic associations with bacteria have facilitated important evolutionary transitions in insects and resulted in long‐term obligate interactions. Recent evidence suggests that these associations ...are not always evolutionarily stable and that symbiont replacement, and/or supplementation of an obligate symbiosis by an additional bacterium, has occurred during the history of many insect groups. Yet, the factors favouring one symbiont over another in this evolutionary dynamic are not well understood; progress has been hindered by our incomplete understanding of the distribution of symbionts across phylogenetic and ecological contexts. While many aphids are engaged into an obligate symbiosis with a single Gammaproteobacterium, Buchnera aphidicola, in species of the Lachninae subfamily, this relationship has evolved into a ‘ménage à trois’, in which Buchnera is complemented by a cosymbiont, usually Serratia symbiotica. Using deep sequencing of 16S rRNA bacterial genes from 128 species of Cinara (the most diverse Lachninae genus), we reveal a highly dynamic dual symbiotic system in this aphid lineage. Most species host both Serratia and Buchnera but, in several clades, endosymbionts related to Sodalis, Erwinia or an unnamed member of the Enterobacteriaceae have replaced Serratia. Endosymbiont genome sequences from four aphid species confirm that these coresident symbionts fulfil essential metabolic functions not ensured by Buchnera. We further demonstrate through comparative phylogenetic analyses that cosymbiont replacement is not associated with the adaptation of aphids to new ecological conditions. We propose that symbiont succession was driven by factors intrinsic to the phenomenon of endosymbiosis, such as rapid genome deterioration or competitive interactions between bacteria with similar metabolic capabilities.
see also the Perspective by Russell et al
Summary
Background
One‐third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti‐TNFs do not respond to treatment, and a relevant proportion experience loss of response or ...intolerance.
Aim
To investigate the efficacy and safety of a second anti‐TNF agent after primary/secondary failure or intolerance to a first drug.
Methods
Inclusion criteria: studies evaluating the efficacy of infliximab (IFX), adalimumab (ADA) and certolizumab‐pegol (CZP) as the second anti‐TNF in CD or UC. Search strategy: Bibliographical searches (PubMed/Embase). Data synthesis: percentage of response/remission; the meta‐analysis was performed using the inverse variance method.
Results
We included 46 studies (37 CD, 8 UC, 1 pouchitis). The CD studies comprised 32 switching IFX→ADA, 4 IFX→CZP and 1 ADA→IFX. Overall, the second anti‐TNF after the failure of IFX in CD induced remission in 43% and response in 63% of patients. The remission rate was higher when the reason to withdraw the first anti‐TNF was intolerance (61%) than after secondary (45%) or primary failure (30%); response rates were, respectively, 72%, 62% and 53%. All UC studies switched IFX→ADA, six of them reporting remission rates ranging from 0% to 50%. Adverse events rate ranged from 0% to 81% in CD, most of them mild (serious adverse event 0–21%, discontinuation rate <20%).
Conclusions
The efficacy of a second anti‐TNF in CD patients largely depends on the cause for switching. The remission rate is higher when the reason to withdraw the first anti‐TNF is intolerance (61%), compared with secondary (45%) or primary failure (30%). Further studies of switch ADA→IFX are needed to evaluate this strategy. PROSPERO‐registry‐number: CRD42014012943.
Atopic dermatitis (AD) is a common disease with a broad spectrum of clinical manifestations. AD can manifest differently in adults than children. Core AD features are similar between children and ...adults overall, including lesions affecting flexural areas, presence of atopy, and xerosis. Adults have more signs of chronic disease, higher prevalence and different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors, whereas children with AD have more exudative lesions, perifollicular accentuation, pityriasis alba, Dennie–Morgan folds, and seborrheic dermatitis‐like presentation. These differences may be due in part to pathophysiologic differences in AD in children compared with adults. Atopic diseases commonly co‐occur with AD, although most do not temporally have the “atopic march.” Further research is warranted to better understand the differential roles of immune dysregulation, epidermal‐barrier disruption, and dysbiosis between children and adults and determine whether such differences translate into differences in therapeutic efficacy.
The use of orange wastes, generated in the orange juice industry, for removing cadmium from aqueous solutions has been investigated. The material was characterized by Fourier transform infrared ...spectroscopy and batch experiments were conducted to determine the adsorption capacity of the biomass. A strong dependence of the adsorption capacity on pH was observed, the capacity increasing as pH value rose. Kinetics and adsorption equilibrium were studied at different pH values (4–6). The adsorption process was quick and the equilibrium was attained within 3
h. The maximum adsorption capacity of orange waste was found to be 0.40, 0.41 and 0.43
mmol/g at pH 4–6, respectively. The kinetic data were analysed using various kinetic models – pseudo-first order equation, pseudo-second order equation, Elovich equation and intraparticle diffusion equation – and the equilibrium data were tested using four isotherm models – Langmuir, Freundlich, Sips and Redlich–Peterson. The data were fitted by non-linear regression and five error analysis methods were used to evaluate the goodness of the fit. The Elovich equation provides the greatest accuracy for the kinetic data and the Sips model the closest fit for the equilibrium data.
Summary
Background
The discontinuation of anti‐tumour necrosis factor (anti‐TNF) treatment in inflammatory bowel disease (IBD) patients in remission could be considered.
Aim
To evaluate the factors ...associated with relapse of IBD after discontinuation of anti‐TNF therapy.
Methods
Electronic (PubMed/Embase) and manual search up to January 2015.
Results
The overall risk of relapse after discontinuation of anti‐TNFs (27 studies) was 44% for Crohn's disease (CD; follow‐up range: 6–125 months) and 38% for ulcerative colitis (follow‐up range: 6–24 months). Several factors were investigated to identify patients who are more likely to achieve long‐lasting remission after anti‐TNF discontinuation. The factors associated with a higher risk of relapse are younger age, smoking, longer disease duration, and fistulising perianal CD. Laboratory markers such as low haemoglobin levels, high C‐reactive protein levels and high faecal calprotectin seem to increase the risk of relapse. On the other hand, low serum anti‐TNF levels seem to be associated with a lower risk of flare‐up. Mucosal healing seems to decrease the risk of relapse after anti‐TNF discontinuation (overall, this risk is 26% at 1 year with mucosal healing and 42% without), although this observation has not been confirmed by some authors. In patients receiving escalated anti‐TNF doses or receiving anti‐TNFs for the prevention of post‐operative CD recurrence, the risk of relapse after discontinuation is high (>75%). Re‐administration of the drug in those who relapsed after stopping treatment is effective and safe.
Conclusions
A high proportion of patients with IBD relapse after discontinuation of anti‐TNF treatment. As available data are insufficient to make strong recommendations on when anti‐TNF therapy could be stopped, decisions should be taken on an individual basis.
The horizontal branch (HB) morphology of globular clusters (GCs) is most strongly influenced by metallicity. The second parameter phenomenon, first described in the 1960s, acknowledges that ...metallicity alone is not enough to describe the HB morphology of all GCs. In particular, astronomers noticed that the outer Galactic halo contains GCs with redder HBs at a given metallicity than are found inside the solar circle. Thus, at least a second parameter was required to characterize HB morphology. While the term 'second parameter' has since come to be used in a broader context, its identity with respect to the original problem has not been conclusively determined. Here we analyze the median color difference between the HB and the red giant branch, hereafter denoted as Delta *D(V - I), measured from Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) photometry of 60 GCs within ~20 kpc of the Galactic center. Analysis of this homogeneous data set reveals that, after the influence of metallicity has been removed from the data, the correlation between Delta *D(V - I) and age is stronger than that of any other parameter considered. Expanding the sample to include HST ACS and Wide Field Planetary Camera 2 photometry of the six most distant Galactic GCs lends additional support to the correlation between Delta *D(V - I) and age. This result is robust with respect to the adopted metallicity scale and the method of age determination, but must bear the caveat that high-quality, detailed abundance information is not available for a significant fraction of the sample. Furthermore, when a subset of GCs with similar metallicities and ages is considered, a correlation between Delta *D(V - I) and central luminosity density is exposed. With respect to the existence of GCs with anomalously red HBs at a given metallicity, we conclude that age is the second parameter and central density is most likely the third. Important problems related to HB morphology in GCs, notably multi-modal distributions and faint blue tails, remain to be explained.
Experimental evidence demonstrating that anomalous localization of waves can be induced in a controllable manner is reported. A microwave waveguide with dielectric slabs randomly placed is used to ...confirm the presence of anomalous localization. If the random spacing between slabs follows a distribution with a power-law tail (Lévy-type distribution), unconventional properties in the microwave-transmission fluctuations take place revealing the presence of anomalous localization. We study both theoretically and experimentally the complete distribution of the transmission through random waveguides characterized by α=1/2 ("Lévy waveguides") and α=3/4, α being the exponent of the power-law tail of the Lévy-type distribution. As we show, the transmission distributions are determined by only two parameters, both of them experimentally accessible. Effects of anomalous localization on the transmission are compared with those from the standard Anderson localization.
Mitofusin 2 (Mfn2) plays a major role in mitochondrial fusion and in the maintenance of mitochondria-endoplasmic reticulum contact sites. Given that macrophages play a major role in inflammation, we ...studied the contribution of Mfn2 to the activity of these cells. Pro-inflammatory stimuli such as lipopolysaccharide (LPS) induced Mfn2 expression. The use of the Mfn2 and Mfn1 myeloid-conditional knockout (KO) mouse models reveals that Mfn2 but not Mfn1 is required for the adaptation of mitochondrial respiration to stress conditions and for the production of reactive oxygen species (ROS) upon pro-inflammatory activation. Mfn2 deficiency specifically impairs the production of pro-inflammatory cytokines and nitric oxide. In addition, the lack of Mfn2 but not Mfn1 is associated with dysfunctional autophagy, apoptosis, phagocytosis, and antigen processing. Mfn2floxed;CreLysM mice fail to be protected from Listeria, Mycobacterium tuberculosis, or LPS endotoxemia. These results reveal an unexpected contribution of Mfn2 to ROS production and inflammation in macrophages.
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•In macrophages, LPS-induced ROS production requires mitochondrial mitofusin 2•Mfn2 is required for the production of cytokines, phagocytosis, and antigen processing•Survival from bacterial infection or septic shock is compromised in Mfn2−/− mice
Tur et al. show that LPS-induced stress in macrophages requires mitofusin 2, which affects mitochondrial respiration and ROS production. The lack of Mfn2 in macrophages blocks the triggering of pro-inflammatory responses, phagocytosis, and antigen presentation.
Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA ...metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca
influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca
influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity.
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