Effect of an endotoxicosis on the vegetative status of patients with chronic pancreatitis

Background. One of the defining typical clinical and pathogenetic syndromes of the formation and severity of chronic pancreatitis (CP) are the syndromes of endogenous intoxication (SEI) and autonomic (vegetative) dysfunction (VD). We did not find any studies of hematological indices of inflammation and intoxication, and especially in comparison with the parameters of vegetative status in CP, which motivated us to conduct this research work. The purpose of the study was to establish the relationship between hematological indices of inflammation and intoxication and the parameters of the autonomic status of patients with chronic pancreatitis. Materials and methods. We examined 69 patients diagnosed with CP who were treated as out-patient. The following hematological indices were determined: leukocyte intoxication index (LII), adaptation index (IA) with subsequent determination of the type of nonspecific adaptive response, lymphocyte-granulocyte index (ILG). The correlations of LII with the parameters of psycho-emotional state (neuroticism, reactive (RA) and personal (PA) anxiety according to the Eisenk, Spielberger-Khanin questionnaires), VD according to the Wayne questionnaire, and the duration of the disease were studied. Results. 63% of patients with chronic pancreatitis were diagnosed with endogenous intoxication of mild and moderate severity according to the Kalf-Khalif index, which makes it necessary to use drugs aimed at its correction. Significant correlations were established between LII and personal anxiety (direct weak r = 0.23, p <0.05), neuroticism (direct moderate force r = 0.41, p <0.05), autonomic dysfunction (direct weak r = 0,1, p <0,05), duration of the disease (direct weak r = 0,15, p <0,05), structural condition of the pancreas by ultrasound manifestations in points (direct weak r = 0.29, p <0.05), the level of α-amylase of the pancreas (direct medium strength r = 0.30, p <0.05). The obtained results proved the presence of significant interactions between the parameters of inflammation and endotoxicosis with indicators of autonomic status and the state of the pancreas. This makes it necessary to prescribe anti-inflammatory and vegetotropic drugs to patients with CP to enhance protocol treatment. Conclusions. Among patients with CP, favorable adaptive reactions were observed in only 36% of subjects, adverse - in 25%, intermediate - in 39%, and the average value of the adaptation index was - 0.48 ± 0.18, which corresponds to the upper limit of the orientation reaction. This motivates additional prescription of vegetotropic and adaptogenic drugs to such patients with CP. Only in 10% of patients with chronic pancreatitis the general immune response has no deviations from the adequate immune response, in 48% of subjects there is an inability of the immune system to complete inflammation, in 42% - the predominance of autoimmune intoxication, which requires enhanced anti-inflammatory therapy.

Climate Change and Vulnerability: The Case of MENA Countries

Climate is changing and mitigation of the corresponding impacts requires assessment of vulnerability and adaptation building. This issue is particularly important in Middle East and North Africa (MENA), which is recognized as one of the most water scarce regions of the world and vulnerable to climate change. Therefore, the objective of this study was an assessment of the different sectors’ vulnerability as well as the overall vulnerability of the MENA countries to climate change. The Notre Dame-Global Adaptation Index (ND-GAIN) was used to investigate climate change vulnerability. Cluster analysis revealed the very high, high, medium and low levels of vulnerability for the MENA countries by distinguishing their extent of exposure, sensitivity and adaptive capacity. Further results indicated that the MENA countries have an acceptable status of infrastructure and habitat, tolerable health and ecosystem statuses, and inappropriate water and food conditions. Water shortage is also a serious problem in this region, to the extent that it is often assumed that water shortage is the root cause of all other types of vulnerability in MENA. However, the obtained results do not support this assumption. These findings provide insight about the adaptation challenges that should be faced and the choices that should be made in response to climate change, in MENA.

ICOR: Improving codon optimization with recurrent neural networks

In protein sequences—as there are 61 sense codons but only 20 standard amino acids—most amino acids are encoded by more than one codon. Although such synonymous codons do not alter the encoded amino acid sequence, their selection can dramatically affect the expression of the resulting protein. Codon optimization of synthetic DNA sequences is important for heterologous expression. However, existing solutions are primarily based on choosing high-frequency codons only, neglecting the important effects of rare codons. In this paper, we propose a novel recurrent-neural-network based codon optimization tool, ICOR, that aims to learn codon usage bias on a genomic dataset of Escherichia coli. We compile a dataset of over 7,000 non-redundant, high-expression, robust genes which are used for deep learning. The model uses a bidirectional long short-term memory-based architecture, allowing for the sequential context of codon usage in genes to be learned. Our tool can predict synonymous codons for synthetic genes toward optimal expression in Escherichia coli. We demonstrate that sequential context achieved via RNN may yield codon selection that is more similar to the host genome, therefore improving protein expression more than frequency-based approaches. ICOR is evaluated on 1,481 Escherichia coli genes as well as a benchmark set of 40 select DNA sequences whose heterologous expression has been previously characterized. ICOR's performance across five metrics is compared to that of five different codon optimization techniques. The codon adaptation index -- a metric indicative of high real-world expression -- was utilized as the primary benchmark in this study. ICOR is shown to improve the codon adaptation index by 41.69% and 17.25% compared to the original and Genscript's GenSmart-optimized sequences, respectively. Our tool is provided as an open-source software package that includes the benchmark set of sequences used in this study.

Immunogenic Potency of a Chimeric Protein Comprising InvH and IpaD against Salmonella and Shigella spp

Shigella and Salmonella cause serious problems in many subjects, including young children and the elderly, especially in developing countries. Chimeric proteins carrying immunogens increase immune response. In-silico tools are applied to design vaccine candidates. Invasion plasmid antigens D (ipaD) gene is one of the Shigella virulence factors. The N-terminal region of the IpaD plays a significant role in invading the host cell. Invasion protein H (invH) gene plays important role in bacterial adherence and entry into epithelial cells. A recombinant chimeric construct, containing IpaD and InvH was designed and used as a vaccine candidate against Shigella and Salmonella enteritidis. After bioinformatics assessments, the construct was designed, synthesized, and expressed in E.coli. Chimeric protein, IpaD, and InvH were purified with Ni-NTA chromatography. Purified proteins were confirmed with western blotting and then were injected into separate mice groups. The antibody titer was estimated with an enzyme-linked immunosorbent assay (ELISA). Mice were challenged with 10, 100, and 1000 LD50 of Salmonella, and the sereny test was performed for Shigella. The Codon adaptation index of the chimeric gene was increased to 0.84. Validation results showed that 97.9% of residues lie in the favored or additional allowed region of the Ramachandran plot. A significant antibody rise was observed in all test groups. The immunized mice with chimer and InvH could tolerate 100 LD50 of Salmonella. In the sereny test, the application of bacteria treated with immunized mice sera of both antigens showed no infection in Guinea pigs' eyes. The recombinant protein could protect animal models against Salmonella and Shigella and therefore can be considered as a suitable vaccine candidate against these two pathogens.

Brief Communication: Piloting a Climate-Change Adaptation Index on US National Forest Lands

Climate change presents a novel and significant threat to the sustainability of forest ecosystems worldwide. The United States Forest Service (USFS) has conducted climate change vulnerability assessments for much of the 193 million acres of national forest lands it manages, yet little to no research exists on the degree to which management units have adopted considerations of climate change into planning or project implementation. In response to this knowledge gap, we piloted a survey instrument in USFS Region 1 (Northern region) and Region 6 (Pacific Northwest region) to determine criteria for assessing the degree to which national forests integrate climate-change considerations into their management planning and activities. Our resulting climate-change adaptation index provides an efficient quantitative approach for identifying where, how, and, potentially, why some national forests are making more progress toward incorporating climate-change adaptations into forest planning and management. Study Implications We used a self-assessment survey of planners and managers on US National Forests in Forest Service Regions 1 and 6 to design a climate change adaptation index for measuring the degree to which national forests units have integrated considerations of climate change into their planning and management activities. Our resulting index can potentially be used to help understand how and why the USFS’s decentralized climate-change adaptation strategy has led some national forests to make comparatively significant progress towards adapting to climate change while others have lagged behind.

Context-dependent and -independent selection on synonymous mutations revealed by 1,135 genomes of Arabidopsis thaliana

Background Synonymous mutations do not alter the amino acids and therefore are regarded as neutral for a long time. However, they do change the tRNA adaptation index (tAI) of a particular codon (independent of its context), affecting the tRNA availability during translation. They could also change the isoaccepting relationship with its neighboring synonymous codons in particular context, which again affects the local translation process. Evidence of selection pressure on synonymous mutations has emerged. Results The proposed selection patterns on synonymous mutations are never formally and systematically tested in plant species. We fully take advantage of the SNP data from 1,135 A. thaliana lines, and found that the synonymous mutations that increase tAI or the isoaccepting mutations in isoaccepting codon context tend to have higher derived allele frequencies (DAF) compared to other synonymous mutations of the opposite effects. Conclusions Synonymous mutations are not strictly neutral. The synonymous mutations that increase tAI or the isoaccepting mutations in isoaccepting codon context are likely to be positively selected. We propose the concept of context-dependent and -independent selection on synonymous mutations. These concepts broaden our knowledge of the functional consequences of synonymous mutations, and should be appealing to phytologists and evolutionary biologists.

Blood Leukocytes in Young and Aged Rats After Whole Body Cryostimulation (–120°C)

The whole body cryostimulation (WBC) (–120°C) induces significant changes in blood leukocyte parameters in young and aged rats (total leukocyte number (leukocytosis or leukopenia); quantitative and qualitative correlation of their types, and shift direction in leukocyte formula); appearance of immature, plasm and polychromatophilic cells, cytoplasm plasmatization in some leukocytes, and changes in the integral leukocyte indices. The direction and severity of these changes depend on animals age (6–7 or 18–20 months old), number of the WBC sessions (1, 2 or 3), terms of observation (day and week) and mainly indicates physiological alterations in a body, that may be associated with the strain of involved functional systems and stress. In aged rats only, 24 hrs after the 2nd WBC session the lymphocyte percentage corresponded to a lower control value, thus indicating the training response formation at this stage. The integral leukocyte indices of aged rats underwent considerably smaller changes if compared with the young ones, especially in 24 hrs and a week after the WBC; the Garkavi adaptation index increased only in aged rats and just 24 hrs after the 3rd WBC session.

Massively parallel gene expression variation measurement of a synonymous codon library

Background Cell-to-cell variation in gene expression strongly affects population behavior and is key to multiple biological processes. While codon usage is known to affect ensemble gene expression, how codon usage influences variation in gene expression between single cells is not well understood. Results Here, we used a Sort-seq based massively parallel strategy to quantify gene expression variation from a green fluorescent protein (GFP) library containing synonymous codons in Escherichia coli. We found that sequences containing codons with higher tRNA Adaptation Index (TAI) scores, and higher codon adaptation index (CAI) scores, have higher GFP variance. This trend is not observed for codons with high Normalized Translation Efficiency Index (nTE) scores nor from the free energy of folding of the mRNA secondary structure. GFP noise, or squared coefficient of variance (CV2), scales with mean protein abundance for low-abundant proteins but does not change at high mean protein abundance. Conclusions Our results suggest that the main source of noise for high-abundance proteins is likely not originating at translation elongation. Additionally, the drastic change in mean protein abundance with small changes in protein noise seen from our library implies that codon optimization can be performed without concerning gene expression noise for biotechnology applications.