Impact of hydroxyurea therapy on serum fatty acids of β-thalassemia patients

Introduction and objective

Fatty acids (FAs) influence cell and tissue metabolism, function, responsiveness to hormonal and other signals in addition to maintenance of membrane integrity of cells. β-Thalassemia is a prevalent inherited blood disorder characterized by abnormal red cell membrane structure and function. Induction of HbF by hydroxyurea (HU) is an enduring therapeutic intervention to manage this. Therefore, in the present study we have carried out the quantification of thirteen free fatty acids to disclose the prognosis of HU in β-thalassemia.

Methods

FAs quantification was carried out using GC–MRM–MS method in the serum of 98 cases of β-thalassemia patients and out of which samples from 34 patients were collected before and after treatment with HU in addition to healthy controls (n?=?31).

Results

Using the combination of random forest (RF) with GC–MRM–MS we were able to establish a classification and prediction model that can discriminate the β-thalassemia from healthy as well as from HU treated group. Docosanoic acid (C-22:0) was most significantly altered in β-thalassemia as compared to healthy at p-value of 8.3?×?10^?09 while erucic acid (C-22:1 Δ^cis-13) can be used as potential marker of HU prognosis because its level became significantly dissimilar at p-value of 3.7?×?10^?04 in same patients in response to HU. However, nervonic acid (C-24:1 Δ^cis-15) was found to be the key player in effectively separating three groups.

Conclusion

In inference, we have noticed that HU therapy also rectifies the serum fatty acid profile in addition to its reported affect i.e. HbF induction in β-thalassemia patients.

     

Protection of IFNAR (?/?) Mice against Bluetongue Virus Serotype 8, by Heterologous (DNA/rMVA) and Homologous (rMVA/rMVA) Vaccination,Expressing Outer-Capsid Protein VP2

The protective efficacy of recombinant vaccines expressing serotype 8 bluetongue virus (BTV-8) capsid proteins was tested in a mouse model. The recombinant vaccines comprised plasmid DNA or Modified Vaccinia Ankara viruses encoding BTV VP2, VP5 or VP7 proteins. These constructs were administered alone or in combination using either a homologous prime boost vaccination regime (rMVA/rMVA) or a heterologous vaccination regime (DNA/rMVA). The DNA/rMVA or rMVA/rMVA prime-boost were administered at a three week interval and all of the animals that received VP2 generated neutralising antibodies. The vaccinated and non-vaccinated-control mice were subsequently challenged with a lethal dose of BTV-8. Mice vaccinated with VP7 alone were not protected. However, mice vaccinated with DNA/rMVA or rMVA/rMVA expressing VP2, VP5 and VP7 or VP2 alone were all protected.     

Point prevalence of gastrointestinal helminthiasis in ruminants in southern Punjab, Pakistan

The present study was carried out to determine the prevalence of gastrointestinal helminthiasis in ruminants in an irrigated area of lower Punjab (Pakistan). For this purpose, 100 faecal samples were collected from sheep, goats, cattle and buffaloes. Parasitological procedures including direct and indirect methods (sedimentation and floatation) and coproculture were used for the identification of helminths. The overall prevalence of helminthiasis was 51% in cattle, 47% in buffaloes, 62% in sheep and 52% in goats, with nematodes being the most common helminths. The prevalence of helminths was higher in young animals compared with adults in cattle (P < 0.0001), buffaloes (P < 0.0001), sheep (P < 0.059) and goats (P = 0.010). The prevalence of different species of helminths also varied in different age groups, with Toxocara vitulorum being higher in calves than adults both in cattle (P = 0.017) and buffaloes (P < 0.0001). Sex-wise prevalence of helminths was higher in males than females for buffaloes (P < 0.0001) and sheep (P = 0.014) in contrast to cattle and goats.     

Effect of aniline coupling on kinetic and thermodynamic properties of Fusarium solani glucoamylase

Purified glucoamylase (GA) from Fusarium solani was chemically modified by cross-linking with aniline hydrochloride in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) for 1 [aniline-coupled glucoamylase-1 (ACG-1)], 7 (ACG-7), and 13 min (ACG-13). The aniline coupling of GA had a profound enhancing effect on temperature, pH optima, and pK _a’s of active site residues. The specificity constants (K _cat/K _m) of native, ACG-1, ACG-7, and ACG-13 were 136, 244, 262, and 208 at 55°C for starch, respectively. The enthalpy of activation (ΔH*) and free energy of activation (ΔG*) for soluble starch hydrolysis were lower for the chemically modified forms compared to native GA. Proteolysis of ACGs by α-chymotrypsin and subtilisin resulted in activation.     

MAPK cascades and major abiotic stresses

Plants have evolved with complex signaling circuits that operate under multiple conditions and govern numerous cellular functions. Stress signaling in plant cells is a sophisticated network composed of interacting proteins organized into tiered cascades where the function of a molecule is dependent on the interaction and the activation of another. In a linear scheme, the receptors of cell surface sense the stimuli and convey stress signals through specific pathways and downstream phosphorylation events controlled by mitogen-activated protein (MAP) kinases and second messengers, leading to appropriate adaptive responses. The specificity of the pathway is guided by scaffolding proteins and docking domains inside the interacting partners with distinctive structures and functions. The flexibility and the fine-tuned organization of the signaling molecules drive the activated MAP kinases into the appropriate location and connection to control and integrate the information flow. Here, we overview recent findings of the involvement of MAP kinases in major abiotic stresses (drought, cold and temperature fluctuations) and we shed light on the complexity and the specificity of MAP kinase signaling modules.     

Patterns of sickle cell, thalassaemia and glucose-6-phosphate dehydrogenase deficiency genes in north-western Saudi Arabia

This study was conducted on 429 blood samples collected from Saudi males and females from Al-Ula in the north-western province of Saudi Arabia in order to determine the frequency of the sickle cell gene, glucose-6-phosphate dehydrogenase (G6PD) deficiency gene, and alpha- and beta-thalassaemia genes, and to investigate the pattern of their interactions. The frequency of the sickle cell gene was 0.0785, while that of the beta-thalassaemia gene was 0.1195. Heterozygous alpha-thalassaemia 2 (- alpha/alpha alpha) was encountered at a frequency of 0.121, while homozygous alpha-thalassaemia 2 (- alpha/- alpha) occurred at a frequency of 0.0046. HbH disease and hydrops fetalis were not encountered. One case with triple alpha-gene arrangement, alpha alpha alpha anti-3.7, was identified. The G6PD deficiency gene frequency was 0.08 and 0.032 in males and females, respectively. Several cases with 2 abnormal genes were encountered. The haematological and biochemical data from the patients with sickle cell disease suggest that the disease in this population is more severe in comparison with cases reported from the eastern population.     

New species and new records of species of Cloacina von Linstow, 1898 (Nematoda: Strongylida) parasitic in the western scrub wallaby,Notamacropus irma (Jourdan) (Marsupialia: Macropodidae) from Western Australia

Systematic Parasitology - The helminth parasites of the western scrub wallaby or black-glove wallaby, Notamacropus irma (Jourdan) which occurs in Western Australia are relatively poorly documented....