Studies on the biosynthesis of antibiotics mupirocin and thiomarinol

Biosynthetic steps in the mupirocin (pseudomonic acids) biosynthetic pathway of $Pseudomonas$ $fluorescens$ NCIMB 10586 have already been deduced. Putative functions of most of the genes of $mup$ cluster have been assigned although exact sequence of steps in the pathway and their timings are not yet known. Thiomarinols are another group of anti-bacterials produced by $Pseudoalteromonas$ $sp$. SANK 73390. Very little is known about the biosynthesis of thiomarinols that share striking structural similarity with pseudomonic acids in their polyketide and fatty acid moieties. This similarity is reflected at genetic level as significant similarity in amino acid identity between the products of at least 27 ORFs in these biosynthetic clusters. This project aimed to learn more of biosynthetic steps in the biosynthesis of mupirocin and thiomarinol antibiotics by testing for functional cross-complementation between pair of genes or a group of genes whose products show significant homology. Surprisingly, only two genes $tmlJ$ and $tmlS$ out of nine studied showed complementation in the $mup$ system. Findings suggested protein-protein interactions limited interchangeability of equivalent functions between two biosynthetic systems. It was shown by expressing related genes as groups for complementation in the $mup$ system that it was possible to confirm specificities of such interactions

Clinical potential of sensory neurites in the heart and their role in decision-making

The process of decision-making is quite complex involving different aspects of logic, emotion, and intuition. The process of decision-making can be summarized as choosing the best alternative among a given plethora of options in order to achieve the desired outcome. This requires establishing numerous neural networks between various factors associated with the decision and creation of possible combinations and speculating their possible outcomes. In a nutshell, it is a highly coordinated process consuming the majority of the brain’s energy. It has been found that the heart comprises an intrinsic neural system that contributes not only to the decision-making process but also the short-term and long-term memory. There are approximately 40,000 cells present in the heart known as sensory neurites which play a vital role in memory transfer. The heart is quite a mysterious organ, which functions as a blood-pumping machine and an endocrine gland, as well as possesses a nervous system. There are multiple factors that affect this heart ecosystem, and they directly affect our decision-making capabilities. These interlinked relationships hint toward the sensory neurites which modulate cognition and mood regulation. This review article aims to provide deeper insights into the various roles played by sensory neurites in decision-making and other cognitive functions. The article highlights the pivotal role of sensory neurites in the numerous brain functions, and it also meticulously discusses the mechanisms through which they modulate their effects

Electronic structure of Pr2MnNiO6 from x-ray photoemission, absorption and density functional theory

The electronic structure of double perovskite Pr2MnNiO6 is studied using core x-ray photoelectron spectroscopy and x-ray absorption spectroscopy. The 2p x-ray absorption spectra show that Mn and Ni are in 2+ and 4+ states respectively. Using charge transfer multiplet analysis of Ni and Mn 2p XPS spectra, we find charge transfer energies {\Delta} of 3.5 and 2.5 eV for Ni and Mn respectively. The ground state of Ni2+ and Mn4+ reveal a higher d electron count of 8.21 and 3.38 respectively as compared to the atomic values of 8.00 and 3.00 respectively thereby indicating the covalent nature of the system. The O 1s edge absorption spectra reveal a band gap of 0.9 eV which is comparable to the value obtained from first principle calculations for U-J >= 2 eV. The density of states clearly reveal a strong p-d type charge transfer character of the system, with band gap proportional to average charge transfer energy of Ni2+ and Mn4+ ions.Comment: 18 pages, 9 figure

On the vegetation of Mosor

Im vorliegenden Beitrag wird ein Überblick über die Vegetation des Mosor-Gebirges, die sämtlich zu der mediterranen Region gehört, gegeben. Dies hängt von den klimatischen Verhältnissen bzw. von der geographischen Lage des Mosor-Gebirges, das gänzlich im Hintergrund des zentralen Teiles des mittleren immergrünen Gebietes Kroatiens verläuft, ab. Gewisse Pflanzengesellschaften und einige Pflanzenarten befinden sich hier auf der Nordwest- bzw. Südgrenze ihres Verbreitungsgebietes.Mosor se s obzirom na svoj fitogeografski položaj odlikuje nekim specifičnostima u biljnom pokrovu. Iako ima visinu od 1340 m/nm, vegetacija na Mosoru pripada u cijelosti mediteranskoj regiji. Šumska zajednica Carpinetum orientalis adriaticum zauzima ondje položaje od 400 do 900 m/nm, a zajednica Seslerio-Ostryetum od 900 m/nm naviše. Na obroncima Mosora zajednica Andropogoni-Diplachnetum serotinae dosiže, koliko je dosad poznato, najjužniju granicu svoje raširenosti. S druge strane, zajednica Erico-Cistetum cretici i Brachypodio-Trifolietum stellati imaju, prema dosadašnjim istraživanjima, na području Mosora i široj okolici Splita svoju sjevernu granicu raširenosti. Isto tako, po podacima iz literature, zajednica Campanulo-Moltkietum petraeae ima na Mosoru (uz Kozjak i Dinaru) svoju sjeverozapadnu granicu. Inače biljni pokrov Mosora, iako jako utjecajan, odlikuje se gotovo svim najznačajnijim tipovima vegetacije mediteranske regije.The papeir gives a short survey of the vegetational cover of Mosor, starting from climatozonal vegetation to the various stages of its degradation. In respect to its phytogeographic position, the mountain of Mosor has certain specific features in its vegetational cover. Although the mountain is 1340 m high, the vegetation of Mosor belongs entirely to the Mediterranean region. The forest community Carpinetum orientalis adriaticum is situated here at places between 400 to 900 m above sea, and the community Seslerio-Ostryetum from 900 m upwards. On the slopes of Mosor, the community Andropogoni-Diplachnetum reaches, as far as it is known today, the southernmost border of its distribution. On the other hand, the communities Erico-Cistetum cretici and Brachypodio-Trijolietum stellati reach, according to current investigations, their northern border in the area of Mosor and the wider surroundings of Split. Also, according to the literature, the community Campanulo-Moltkietum petraeae has its north-western border at Mosor (together with Kozjak and Dinara mts). Otherwise the vegetational cover of Mosor, although of great influence, is characterized by all the most significant types of the vegetation of the Mediterranean region

Leprosy drug clofazimine activates peroxisome proliferator-activated receptor-γ and synergizes with imatinib to inhibit chronic myeloid leukemia cells

Leukemia stem cells contribute to drug-resistance and relapse in chronic myeloid leukemia (CML) and BCR-ABL1 inhibitor monotherapy fails to eliminate these cells, thereby necessitating alternate therapeutic strategies for patients CML. The peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone downregulates signal transducer and activator of transcription 5 (STAT5) and in combination with imatinib induces complete molecular response in imatinib-refractory patients by eroding leukemia stem cells. Thiazolidinediones such as pioglitazone are, however, associated with severe side effects. To identify alternate therapeutic strategies for CML we screened Food and Drug Administration-approved drugs in K562 cells and identified the leprosy drug clofazimine as an inhibitor of viability of these cells. Here we show that clofazimine induced apoptosis of blood mononuclear cells derived from patients with CML, with a particularly robust effect in imatinib-resistant cells. Clofazimine also induced apoptosis of CD34+38− progenitors and quiescent CD34+ cells from CML patients but not of hematopoietic progenitor cells from healthy donors. Mechanistic evaluation revealed that clofazimine, via physical interaction with PPARγ, induced nuclear factor kB-p65 proteasomal degradation, which led to sequential myeloblastoma oncoprotein and peroxiredoxin 1 downregulation and concomitant induction of reactive oxygen species-mediated apoptosis. Clofazimine also suppressed STAT5 expression and consequently downregulated stem cell maintenance factors hypoxia-inducible factor-1α and -2α and Cbp/P300 interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2). Combining imatinib with clofazimine caused a far superior synergy than that with pioglitazone, with clofazimine reducing the half maximal inhibitory concentration (IC50) of imatinib by >4 logs and remarkably eroding quiescent CD34+ cells. In a K562 xenograft study clofazimine and imatinib co-treatment showed more robust efficacy than the individual treatments. We propose clinical evaluation of clofazimine in imatinib-refractory CML

IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies

Numerical Modelling of Drag Forces in Micro mechanical Beams Array

Recent thrust in the design of sensitive sensors and actuators have motivated many researchers to optimize various parameters of micro and nano scale devices. It is found that the performance of most of the dynamic sensors is influence by the resonance frequency and quality factor. Since, the quality factor is inversely proportional to different internal and external dissipation mechanisms at that scale, it is imperative to study and control dominant damping mechanism. Fluid damping is found to be the dominant mechanism for the devices which operate at atmospheric pressure.It mainly consists of squeeze film damping and damping due to drag. As the size of mechanical structure reduces, the influence of squeeze- film damping reduces and the drag force becomes dominant.The computation of drag force has been the subject of research since many decades in the field of aerospace engineering. However, it regained renewed interest with the advent of micro and nanotechnology

Assessment of motion and kinematic characteristics of frozen-thawed Sirohi goat semen using computer-assisted semen analysis

Aim: The aim was to determine the motion and kinematics characteristic of frozen-thawed spermatozoa in Sirohi goat using computer-assisted semen analysis. Materials and Methods: A study was carried out in Sirohi buck. Semen collection was made biweekly from each buck with the help of artificial vagina. A total of 12 ejaculates were collected from two bucks (six ejaculates from each buck). Freshly collected semen was pooled and later evaluated. The pooled semen sample was extended with standard glycerolated egg yolk tris extender and later subjected to a process of cryopreservation. The motion and kinematic characteristics of spermatozoa were studied during freez-thawing process. Results: Significantly (p<0.01) higher value of live percent, hypo-osmotic swelling test, and acrosomal integrity were recorded in neat semen followed by diluted and frozen thaw semen. The proportion of spermatozoa showing slow progression were the highest in the neat and diluted semen followed by rapid and non-progressively motile, while a reverse pattern was observed in the frozen thaw semen where the proportion of non-progressively motile spermatozoa were significantly (p<0.01) higher followed by slow and rapid progression. Conclusion: This study showed that the best results for motion, vitality, plasma membrane integrity, and acrosome status were obtained in the neat semen followed by diluted and frozen thaw semen. Further, the process of cryopreservation results in a shift of motility from slow to non-progressive in the post-thaw semen with a significant decrease in the path velocities when compared to neat and diluted semen. Hence, it can be concluded that freezing-thawing process reduces the motility and kinematic characters spermatozoa and may be an important factor affecting the fertilizing ability of spermatozoa resulting in poor conception rate after insemination in goats

Comparative Study on Sports Specific Personality among Male Physical Education Students of Uttar Pradesh

The present study was intended to compare the various sports specific personality (sociability, dominance, extroversion, conventionality, self-concept, mental toughness, and emotional stability) of physical education students of different universities (Agra University, Lucknow University, and Mahatma Gandhi Kashi Vidyapith University, Varanasi) of Uttar Pradesh using sports personality specific test developed by Dr. Agya Jit Singh and H.S. Cheema (2010). Descriptive research design was used in this study. For the purpose of the present study, a total of 90 physical education students were selected through random sampling. The collected data were analyzed using ANOVA. Level of significant was fixed at 0.05. The results of the study indicates that there was a significant difference on extroversion and self-concept between different university’s physical education students, however, no significant difference was found on sociability, dominance, conventionality, mental toughness, and emotional-stability