Small company mergers--good for whom?

An analysis of 105 mergers among small UK biotech companies over a 10-year period shows that the improvement of shareholder positions, rather than product pipelines or business opportunities, is the main motivation for such transactions.     

大肠杆菌Small RNA EsrE的转录调控

【背景】大肠杆菌中Small RNA EsrE调控琥珀酸脱氢酶的表达并影响细胞生长,对其调控机制的探究有利于加深EsrE对细胞生长影响的认识。【目的】探究大肠杆菌Small RNA EsrE的转录调控机制。【方法】通过双质粒报告系统筛选转录调控因子,并通过凝胶迁移实验(electrophoretic mobilityshiftassay,EMSA)和qRT-PCR研究方法验证转录调控因子。【结果】双质粒报告系统证明RNA聚合酶亚基σ~(32) (RpoH)上调P_(esrE),β-羟酰-ACP脱水酶(FabZ)下调PesrE。EMSA结果和体内实验显示RpoH结合P_(esrE)片段,FabZ不结合P_(esrE)片段。【结论】RpoH直接结合启动子序列参与调控,FabZ以其他方式间接参与Small RNA EsrE的转录调控。     

Small animal model for HIV-1 Disease

Development of a viral infection model of the humanimmune systemusingsmall animalsis animportant goal in biomedi-cal research,especiallyinstudiesof HIV-1infection.Thisis particularlyimportant since susceptibilityto HIV-1islimit-edto humans.The C.B-17-scid/scid-mouselacks mature Tand Bcells dueto a defective rearrangement of the Tcell re-ceptor andimmunoglobulin genes.Twotypes of humanlymphoid chimeras have been establishedin scid-mice.The firstsuccess withthe human mouse chimera was achie…     

Small：病毒样颗粒示踪研究取得新进展

近日来自中科院长春应用化学研究所的研究人员在病毒样颗粒示踪研究方面取得重要进展，相关成果发表在国际著名期刊Small上，并被选为杂志封面文章。     

‘Small Data’ for big insights in ecology

Big Data science has significantly furthered our understanding of complex systems by harnessing large volumes of data, generated at high velocity and in great variety. However, there is a risk that Big Data collection is prioritised to the detriment of ‘Small Data’ (data with few observations). This poses a particular risk to ecology where Small Data abounds. Machine learning experts are increasingly looking to Small Data to drive the next generation of innovation, leading to development in methods for Small Data such as transfer learning, knowledge graphs, and synthetic data. Meanwhile, meta-analysis and causal reasoning approaches are evolving to provide new insights from Small Data. These advances should add value to high-quality Small Data catalysing future insights for ecology.     

Small：病毒样颗粒示踪研究取得新进展

近日来自中科院长春应用化学研究所的研究人员在病毒样颗粒示踪研究方面取得重要进展。相关成果发表在国际著名期刊Small上。并被选为杂志封面文章。     

Small autocatalytic reaction networks—III. Monotone growth functions

The classification of the dynamical behaviour of first order replicator equations is extended to models with monotonical growth rates. It is shown that for two species there is a general classification independent of the particular form of the growth function. For three species a common dynamical behaviour for all power laws can be found and the existence of limit cycles is disproved. For more general growth functions, however, limit cycles may occur.     

The Small β-Barrel Domain: A Survey-Based Structural Analysis

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How Small Are the Smallest Selectable Domains of Form?

Two lines of Drosophila melanogaster from the same base population were selected in opposite directions to produce simultaneous antagonistic changes in two very small (less than 0.2 mm) and closely adjacent (less than 0.3 mm) dimensions within the base of the wing. Wing dimensions near the targeted area became differentiated by large positive and negative percentage differences, while only small homogeneous percentage changes occurred in the remainder of the wing. If very small regions of morphology (less than 100 cells across) can respond to selection almost independently, even in small population samples, then the control of developmental detail must involve many genes, and the diversity of possible outcomes in development and adaptation must be large.     

Could Small Neurotoxins-Peptides be Expressed during SARS-CoV-2 Infection?

SARS-CoV-2 pathogenesis has been recently extended to human central nervous system (CNS), in addition to nasopharyngeal truck, eye, lung and gut. The recent literature highlights that some SARS-CoV-2 spike glycoprotein regions homologous to neurotoxin-like peptides might bind to human nicotinic Acetyl-Choline Receptors (nAChRs). Spike-nAChR interaction can probably cause dysregulation of CNS and cholinergic anti-inflammatory pathways and uncontrolled immune-response, both associated to a severe COVID-19 pathophysiology. Herein, we hypothesize that inside the Open Reading Frame (ORF) region of spike glycoprotein, the RNA polymerase can translate small neurotoxic peptides by means of a “jumping mechanism” already demonstrated in other coronaviruses. These small peptides can bind the snAChRs instead of Spike glycoproteins. A striking homology occurred between these small peptides observed by sequence retrieval and proteins alignment. Acting as nAChRs antagonists, these small peptides (conotoxins) could be the explanation for the extrapulmonary clinical manifestations (neurological, hemorrhagic and thrombotic expressions, the prolonged apnea, the cardiocirculatory collapse, the heart arrhythmias, the ventricular tachycardia, the body temperature alteration, the electrolyte K+ imbalance and finally the significant reduction of butyryl cholinesterase (BuChE) plasma levels, as observed in COVID-19 patients. Several factors might induce the expression of these small peptides, including microbiota. The main hypothesis regarding the presence of these small peptides opens a new scenario on the etiology of COVID-19 clinical symptoms observed so far, including the neurological manifestations.     

β-Glucosidase Activity in the Rat Small Intestine toward Quercetin Monoglucosides

In order to evaluate the positional specificity for a glucoside group in the hydrolysis of flavonoid glucosides in the rat small intestine, β-glucosidase activity was measured with the quercetin monoglucosides, quercetin-3-O-β-D-glucopyranoside (Q3G), quercetin-4′-O-β-D-glucopyranoside (Q4′G) and quercetin-7-O-β-D-glucopyranoside (Q7G), as well as with quercetin-3-O-rutinoside (rutin) and p-nitrophenyl-β-D-glucopyranoside (NPG) by using the HPLC technique. Enzymes were prepared from rat small intestinal mucosa of the duodenum, jejunum and ileum, among which the enzyme activity of the jejunum was highest for all the glycosides tested. Q4′G was the richest substrate for a β-glucosidase solution among these glycosides, while rutin and NPG were both poor substrates. This suggests that dietary flavonoid glucosides are primarily hydrolyzed and liberated aglycones in the jejunum.     

Inhibition of Aggregation of Amyloid β42 by Arginine-Containing Small Compounds

Aggregations of proteins are in many cases associated with neurodegenerative diseases such as Alzheimer’s (AD). Small compounds capable of inhibiting protein aggregation are expected to be useful for not only in the treatment of disease but also in probing the structures of aggregated proteins. In previous studies using phage display, we found that arginine-rich short peptides consisting of four or seven amino acids bound to soluble 42-residue amyloid β (Aβ42) and inhibited globulomer (37/48 kDa oligomer) formation. In the present study, we searched for arginine-containing small molecules using the SciFinder searching service and tested their inhibitory activities against Aβ42 aggregation, by sodium dodecyl sulfate (SDS)-PAGE and thioflavine T binding assay. Commercially available Arg-Arg-7-amino-4-trifluoromethylcoumarin was found to exhibit remarkable inhibitory activities to the formation of the globulomer and the fibril of Aβ42. This chimera-type tri-peptide is expected to serve as the seed molecule of a potent inhibitor of the Aβ aggregation process.     

Why Was the 2009 Influenza Pandemic in England So Small?

The "Swine flu" pandemic of 2009 caused world-wide infections and deaths. Early efforts to understand its rate of spread were used to predict the probable future number of cases, but by the end of 2009 it was clear that these predictions had substantially overestimated the pandemic's eventual impact. In England, the Health Protection Agency made announcements of the number of cases of disease, which turned out to be surprisingly low for an influenza pandemic. The agency also carried out a serological survey half-way through the English epidemic. In this study, we use a mathematical model to reconcile early estimates of the rate of spread of infection, weekly data on the number of cases in the 2009 epidemic in England and the serological status of the English population at the end of the first pandemic wave. Our results reveal that if there are around 19 infections (i.e., seroconverters) for every reported case then the three data-sets are entirely consistent with each other. We go on to discuss when in the epidemic such a high ratio of seroconverters to cases of disease might have been detected, either through patterns in the case reports or through even earlier serological surveys.     

Small molecules interacting with α-synuclein: antiaggregating and cytoprotective properties

Curcumin, a dietary polyphenol, has shown a potential to act on the symptoms of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, as a consequence of its antioxidant, anti-inflammatory and anti-protein aggregation properties. Unfortunately, curcumin undergoes rapid degradation at physiological pH into ferulic acid, vanillin and dehydrozingerone, making it an unlikely drug candidate. Here, we evaluated the ability of some curcumin by-products: dehydrozingerone (1), its O-methyl derivative (2), zingerone (3), and their biphenyl analogues (4–6) to interact with α-synuclein (AS), using CD and fluorescence spectroscopy. In addition, the antioxidant properties and the cytoprotective effects in rat pheochromocytoma (PC12) cells prior to intoxication with H₂O₂, MPP+ and MnCl₂ were examined while the Congo red assay was used to evaluate the ability of these compounds to prevent aggregation of AS. We found that the biphenyl zingerone analogue (6) interacts with high affinity with AS and also displays the best antioxidant properties while the biphenyl analogues of dehydrozingerone (4) and of O-methyl-dehydrozingerone (5) are able to partially inhibit the aggregation process of AS, suggesting the potential role of a hydroxylated biphenyl scaffold in the design of AS aggregation inhibitors.     

Investigation of Atomic Level Patterns in Protein—Small Ligand Interactions

Background

Shape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes.

Methodology and Principal Findings

We show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites.

Conclusions and Significance

We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds.