Protein complexes detection based on node local properties and gene expression in PPI weighted networks

Background Identifying protein complexes from protein–protein interaction (PPI) networks is a crucial task, and many related algorithms have been developed. Most algorithms usually employ direct neighbors of nodes and ignore resource allocation and second-order neighbors. The effective use of such information is crucial to protein complex detection. Result Based on this observation, we propose a new way by combining node resource allocation and gene expression information to weight protein network (NRAGE-WPN), in which protein complexes are detected based on core-attachment and second-order neighbors. Conclusions Through comparison with eleven methods in Yeast and Human PPI network, the experimental results demonstrate that this algorithm not only performs better than other methods on 75% in terms of f-measure+, but also can achieve an ideal overall performance in terms of a composite score consisting of five performance measures. This identification method is simple and can accurately identify more complexes.

Biochemical composition of fresh, dried and frozen berries different varieties of sea buckthorn (Hippophae rhanoides L.)

Purpose. Determine the formation of physico-chemical quality indicators (berry weight, protein, carbohydrates, fat, dietary fiber, organic acids) of fresh, dried and frozen sea buckthorn fruits of different varieties. Methods. Laboratory, mathematical and statistical, physicochemical. Results. The water content in sea buckthorn berries was the highest, but also varied significantly depending on the variety. The varieties of sea buckthorn ‘Haleryt’ and ‘Yelyzaveta’ had the highest content – 90%, by 2 and 3% less in the varieties ‘Burshtynove namysto’ and ‘Altaiska’, in the varieties ‘Sonechko’ and ‘Uliublena’ – 85%. The lowest water content was in the berries of ‘Ryzhyk’, ‘Podruha’, ‘Diuimovochka’, ‘Chechek’ varieties – 75–78%. Dried fruits contained water from 22 to 16%. In the varieties ‘Uliublena’, ‘Yelyzaveta’, ‘Altaiska’ – 22%, ‘Haleryt’, ‘Diuimovochka’, ‘Sonechko’, ‘Burshtynove Namysto’ – 20%, ‘Avhustyna’, ‘Ryzhyk’, ‘Podruha’ – 18%, ‘Veleten’ and ‘Chechek’ – 17 and 16%, respectively. The content of dietary fiber was 4.5–6.2% depending on the variety. The lowest content of dietary fiber was found in the varieties ‘Uliublena’ and ‘Altaiska’ – 4.5–4.7% in fresh and 2.4–2.5% in dried berries. The highest rates were in the varieties ‘Avhustyna’, ‘Sonechko’, ‘Burshtynove Namysto’ in fresh varieties – 6.0, 6.2 and 5.9%, and in dried varieties – 5.5%. The ‘Chechek’ and ‘Veleten’ varieties contained 5.7% in fresh berries and 5.0 and 4.5% in dried berries. The content of fat in fresh berries was in the range of 5.0–5.7%, depending on the variety. In dried berries it increased to 6.0–6.7% or 18–20% depending on the variety of sea buckthorn. In fast-freezing berries, this figure decreased to 4.5–5.2% or 9–10%. The content of organic acids in fresh fruits was the highest – 1.5–2.0%, depending on the sea buckthorn variety. Their content in dried berries decreased to 1.3–1.7% except for the varieties ‘Avhustyna’, ‘Sonechko’ and ‘Burshtynove namysto’, and in the frozen ones to 0.3–0.9%. It should be noted that a similar trend is observed in frozen berries of ‘Avhustyna’, ‘Sonechko’ and ‘Burshtynove namysto’ varieties. Conclusions. It is established that physicochemical quality indicators of fresh, dried and frozen sea buckthorn berries vary depending on the variety. The varieties ‘Avhustyna’, ‘Sonechko’, ‘Burshtynove Namysto’ have the largest weight of one berry 1.4–1.5 g. 8–6.0%), fat (5.5–5.7%), protein (1.5%), organic acids (2.0%) and dietary fiber (5.9–6.2%) in fresh berries.

AAC Castle red spring wheat

AAC Castle, an awned hard red spring wheat (Triticum aestivum L.), cultivar, combines high grain yield and good agronomic characteristics with excellent resistance to leaf, stem, stripe rust, common bunt and loose smut. It also expressed tolerance to the orange wheat blossom midge. Based on 39 station years of data in the registration trials from 2014 to 2016, the grain yield of AAC Castle was about 17% higher than 5700PR but similar to the other checks. AAC Castle was significantly shorter than AAC Foray and CDC Terrain, but had similar lodging resistance and maturity. AAC Castle had higher test weight, protein concentration, falling number and flour yield than AAC Foray and CDC Terrain. AAC Castle is eligible for grade of the Canada Prairie Spring Red wheat market class.

Probing allosteric interactions in homo-oligomeric molecular machines using solution NMR spectroscopy

Developments in solution NMR spectroscopy have significantly impacted the biological questions that can now be addressed by this methodology. By means of illustration, we present here a perspective focusing on studies of a number of molecular machines that are critical for cellular homeostasis. The role of NMR in elucidating the structural dynamics of these important molecules is emphasized, focusing specifically on intersubunit allosteric communication in homo-oligomers. In many biophysical studies of oligomers, allostery is inferred by showing that models specifically including intersubunit communication best fit the data of interest. Ideally, however, experimental studies focusing on one subunit of a multisubunit system would be performed as an important complement to the more traditional bulk measurements in which signals from all components are measured simultaneously. Using an approach whereby asymmetric molecules are prepared in concert with NMR experiments focusing on the structural dynamics of individual protomers, we present examples of how intersubunit allostery can be directly observed in high-molecular-weight protein systems. These examples highlight some of the unique roles of solution NMR spectroscopy in studies of complex biomolecules and emphasize the important synergy between NMR and other atomic resolution biophysical methods.

Formulation and evaluation of fast dissolving tablets of captopril

Oral administration is the most popular route for systemic effects due to its ease of ingestion, pain, avoidance, versatility and most importantly, patient compliance. The development of enhanced oral protein delivery technology by mouth dissolving Tablets which may release these drugs in the mouth are very promising for the delivery of high molecular weight protein and peptide. Good mouth feel property of MDDS helps to change the basic view of medication as “bitter pill”, particularly for pediatric patients. To prepare mouth dissolving tablet using SSG & CCM by using Antihypertensive as model drug. Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme and it is a key component of the renin-angiotensin-aldosterone system. The ƛmax of Captopril was determined by scanning the 10µg / ml solution of drug using UV-Spectrophotometer and was found to be 271nm. The linear correlation was found to be 0.9995.The Fast dissolving tablets of captopril were prepared by direct compression method. Captopril can be successfully formulated as mouth dissolving tablets using various super disintegrate in different concentrations by direct compression method. The formulation containing 10% of crospovidone as super disintegrated was found to be outstanding than other formulations in terms of disintegration time and rate of dissolution.

Mesowestern Blot: Simultaneous Analysis of Hundreds of Sub-Microliter Lysates

Western blotting is a widely-used technique for molecular-weight-resolved analysis of proteins and their post-translational modifications, but has been refractory to affordable scale-up. Here, we report the Mesowestern blot, which uses a 3D-printable gel-casting mold to enable affordable, high-throughput Western blotting with standard sample preparation and small (<1 uL) sample sizes. The casted polyacrylamide gel contains 336, 0.5 uL micropipette-loadable sample wells arranged within a standard microplate footprint. Polyacrylamide % can be altered to change molecular weight resolution range. Proof-of-concept experiments using both infrared-fluorescent molecular weight protein ladder as well as cell lysate (RIPA buffer) demonstrate protein loaded in Mesowestern gels is amenable to the standard Western blotting steps. The main difference between Mesowestern and traditional Western is that semi-dry horizontal instead of immersed vertical gel electrophoresis is used. The linear range of detection is approximately 2 orders of magnitude, with a limit of detection (for beta-actin) of around 30 ng of total protein from mammalian cell lysates (~30-3000 cells). Because the gel mold is 3D-printable, users have significant design freedom for custom layouts, and there are few barriers to adoption by the typical cell and molecular biology laboratory already performing Western blots.

Update on Thiamine Triphosphorylated Derivatives and Metabolizing Enzymatic Complexes

While the cellular functions of the coenzyme thiamine (vitamin B1) diphosphate (ThDP) are well characterized, the triphosphorylated thiamine derivatives, thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), still represent an intriguing mystery. They are present, generally in small amounts, in nearly all organisms, bacteria, fungi, plants, and animals. The synthesis of ThTP seems to require ATP synthase by a mechanism similar to ATP synthesis. In E. coli, ThTP is synthesized during amino acid starvation, while in plants, its synthesis is dependent on photosynthetic processes. In E. coli, ThTP synthesis probably requires oxidation of pyruvate and may play a role at the interface between energy and amino acid metabolism. In animal cells, no mechanism of regulation is known. Cytosolic ThTP levels are controlled by a highly specific cytosolic thiamine triphosphatase (ThTPase), coded by thtpa, and belonging to the ubiquitous family of the triphosphate tunnel metalloenzymes (TTMs). While members of this protein family are found in nearly all living organisms, where they bind organic and inorganic triphosphates, ThTPase activity seems to be restricted to animals. In mammals, THTPA is ubiquitously expressed with probable post-transcriptional regulation. Much less is known about the recently discovered AThTP. In E. coli, AThTP is synthesized by a high molecular weight protein complex from ThDP and ATP or ADP in response to energy stress. A better understanding of these two thiamine derivatives will require the use of transgenic models.

Ceftriaxone-induced Encephalopathy: A Pharmacokinetic Approach

We report a case of ceftriaxone-induced encephalopathy correlated with high cerebrospinal fluid concentration. Neurotoxicity of cephalosporin is increasingly reported, especially regarding fourth-generation cephalosporins. The factors influencing the corticospinal fluid (CSF) concentration are plasma concentration, liposolubility, ionization, molecular weight, protein binding and efflux. In our patient, high levels of ceftriaxone (27.9 mg/l) were found in the CSF. β-lactam associated neurotoxicity is mainly related to similarities between GABA and β-lactam ring. Because of disparate CSF/plasma ratio and blood-brain barrier efflux among patients, plasmatic drug monitoring probably cannot be used as a surrogate of CSF concentration. This is, as we know, the first case of described ceftriaxone-induced encephalopathy associated with an objective excessive cerebrospinal concentration.

Evolutionary insights into the microneme-secreted, chitinase-containing high molecular weight protein complexes involved in Plasmodium invasion of the mosquito midgut

While general mechanisms by which Plasmodium ookinetes invade the mosquito midgut have been studied, details remain to be understood regarding the interface of the ookinete, specifically its barriers to invasion, such as the proteolytic milieu, the chitin-containing, protein cross-linked peritrophic matrix, and the midgut epithelium. Here we review knowledge of Plasmodium chitinases and the mechanisms by which they mediate the ookinete crossing the peritrophic matrix. The integration of new genomic insights into previous findings advances our understanding of Plasmodium evolution. Recently obtained Plasmodium spp. genomic data enable identification of the conserved residues in the experimentally demonstrated hetero-multimeric, high molecular weight complex comprised of a short chitinase covalently linked to binding partners, von Willebrand factor A domain-related protein (WARP) and secreted ookinete adhesive protein (SOAP). Artificial intelligence-based high-resolution structural modeling using the DeepMind AlphaFold algorithm yielded highly informative 3D structures and insights into how short chitinases, WARP, and SOAP may interact at the atomic level to form the ookinete-secreted peritrophic matrix invasion complex. Elucidating the significance of the divergence of ookinete-secreted micronemal proteins among Plasmodium species could lead to a better understanding of ookinete invasion machinery and the co-evolution of Plasmodium -mosquito interactions.