ABSTRACT
How do phenotypic associations intrinsic to an organism, such as developmental and mechanical processes, direct morphological evolution? Comparisons of intraspecific and clade-wide patterns of phenotypic covariation could inform how population-level trends ultimately dictate macroevolutionary changes. However, most studies have focused on analyzing integration and modularity either at macroevolutionary or intraspecific levels, without a shared analytical framework unifying these temporal scales. In this study, we investigate the intraspecific patterns of cranial integration in two squamate species: Natrix helvetica and Anolis carolinensis. We analyze their cranial integration patterns using the same high-density three-dimensional geometric morphometric approach used in a prior squamate-wide evolutionary study. Our results indicate that Natrix and Anolis exhibit shared intraspecific cranial integration patterns, with some differences, including a more integrated rostrum in the latter. Notably, these differences in intraspecific patterns correspond to their respective interspecific patterns in snakes and lizards, with few exceptions. These results suggest that interspecific patterns of cranial integration reflect intraspecific patterns. Hence, our study suggests that the phenotypic associations that direct morphological variation within species extend across micro- and macroevolutionary levels, bridging these two scales.
ABSTRACT
Sexual dysfunction in Diabetes is an under-investigated problem, especially in women. The research barriers surrounding the issue of female sexual dysfunction are manifold and difficult to surpass, especially in the context of the Asian Subcontinent, where a multitude of sociocultural factors suppress the expression of distress. Early screening, diagnosis, and counselling can help in managing female sexual dysfunction in Diabetes Mellitus and positively impact the lives of many women. This study was undertaken to find the prevalence of sexual dysfunction among diabetic women of reproductive age group, its relation to BMI, duration of Diabetes and microvascular complications, and to find its sociodemographic associations. MATERIAL: A descriptive, observational study was carried out over a period of 1 year. 250 purposively sampled women attending the diabetic outpatient department of a tertiary care hospital were enrolled. All were known diabetic, between the ages of 30 and 44 years. A detailed history was obtained with the aid of a case record form which included the FSFI (Female Sexual Function Index), and a demographic questionnaire, after proper explanation in their own local vernacular as per their literacy level. Available medical records were used for finding the duration of diabetes, and associated diabetes related microvascular complications. OBSERVATION: Prevalence of FSD among the study population was 73.6%. A significant association was found between age and sexual dysfunction (p<0.05). It was found to be more among the Hindus, compared to the Muslims (p<0.05). There was a significant association with BMI (>25kg/m2), increasing duration of Diabetes, and the presence of microvascular complications (p<0.05). In fact, all patients with microvascular complications were experiencing some degree of sexual dysfunction. No association was found with socioeconomic status, literacy, addiction, occupation or type of family. CONCLUSION: Female sexual health issues in Diabetes are a neglected area, both in the clinic as well as in research, yet sexual health problems in this group may be more common than previously recognised. Low FSFI scores are associated with increasing age, higher BMI and increasing duration of Diabetes. Future studies may identify appropriate ways to probe and explore the related issues for early screening, and help establish the role of newer treatments.
Subject(s)
Diabetes Complications , Diabetes Mellitus , Sexual Dysfunction, Physiological , Adult , Diabetes Complications/complications , Diabetes Mellitus/epidemiology , Female , Humans , Male , Outpatients , Prevalence , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunction, Physiological/etiology , Surveys and Questionnaires , Tertiary Care CentersABSTRACT
Afferent loop syndrome (ALS) is an uncommon complication of gastrojejunostomy. It may be acute or chronic depending on whether symptoms manifest within 7 days of surgery. Rarely acute ALS may give rise to acute pancreatitis. It may present early in the postoperative course and, if diagnosed late, may result in organ failure within 48h. We report a middle-aged woman with carcinoma of the stomach managed by subtotal gastrectomy with Billroth II gastrojejunostomy and Braun jejunojejunostomy. The patient developed vomiting and abdominal pain in the first postoperative day with acute renal shutdown and about 500ml drain output of dirty fluid. On investigation, a diagnosis of acute pancreatitis due to afferent loop syndrome was made, and the patient was resuscitated in the intensive care unit. However, she showed early signs of organ failure and succumbed to her condition within 6 days of surgery. Since the complication is rare following gastrojejunostomy and often mimics ALS, an early diagnosis becomes difficult. If delay in management happens, premature organ failure may lead to high morbidity and mortality.
Subject(s)
Afferent Loop Syndrome , Gastric Bypass , Pancreatitis , Stomach Neoplasms , Female , Humans , Middle Aged , Acute Disease , Afferent Loop Syndrome/diagnosis , Afferent Loop Syndrome/etiology , Afferent Loop Syndrome/surgery , Gastrectomy/adverse effects , Gastric Bypass/adverse effects , Pancreatitis/etiology , Pancreatitis/complications , Postoperative Period , Stomach Neoplasms/surgery , Stomach Neoplasms/complicationsABSTRACT
Relative brain size has long been considered a reflection of cognitive capacities and has played a fundamental role in developing core theories in the life sciences. Yet, the notion that relative brain size validly represents selection on brain size relies on the untested assumptions that brain-body allometry is restrained to a stable scaling relationship across species and that any deviation from this slope is due to selection on brain size. Using the largest fossil and extant dataset yet assembled, we find that shifts in allometric slope underpin major transitions in mammalian evolution and are often primarily characterized by marked changes in body size. Our results reveal that the largest-brained mammals achieved large relative brain sizes by highly divergent paths. These findings prompt a reevaluation of the traditional paradigm of relative brain size and open new opportunities to improve our understanding of the genetic and developmental mechanisms that influence brain size.
ABSTRACT
The lesson learnt from nature is presented through the examination of shells from four mollusc species (two gastropods and two bivalves). Individual aragonite tablets together with the organic network have been studied in terms of tablet dimensions, tablet stacking sequence, texture and the weight fraction of the organic present in these bio-composite shells. Mechanical properties viz. elastic modulus and hardness at the macro (bulk), micro (tablet) and nano (aragonite nanograins) levels have been determined using the experimental technique of nanoindentation together with the theoretical formulations offered by the Mori-Tanaka method and other such mechanical models for composites. XRD studies confirm the strong c-axis crystallographic orientation - aligned parallel to the direction of growth and crystallization of nacreous tablets, and fractography performed on the shell specimens suggests a difference in the stacking of individual aragonite layers for the gastropod and bivalve molluscan class, respectively. DSC and TG-DTA data helped in characterizing the organic material present in the shell specimens and in calculating the organic weight and volume fractions across species. Further to this, the DSC data revealed that the nature of the organic in the brick and mortar assembly of nacre, was similar in nature across the two molluscan classes reported in this study. EBSD studies performed on our system revealed a difference in crystallographic texture for the two different tablet stacking (columnar and sheet nacre). It has been shown experimentally that the shells of gastropods (columnar nacre) are orthotropic in nature, while the bivalve mollusc shells (sheet nacre) are anisotropic in nature.
Subject(s)
Bivalvia , Gastropoda , Nacre , Animals , Calcium Carbonate , CrystallizationABSTRACT
We report the first observation of two wobbling bands in ^{183}Au, both of which were interpreted as the transverse wobbling (TW) band but with different behavior of their wobbling energies as a function of spin. It increases (decreases) with spin for the positive (negative) parity configuration. The crucial evidence for the wobbling nature of the bands, dominance of the E2 component in the ΔI=1 transitions between the partner bands, is provided by the simultaneous measurements of directional correlation from the oriented states ratio and the linear polarization of the γ rays. Particle rotor model calculations with triaxial deformation reproduce the experimental data well. A value of spin, I_{m}, has been determined for the observed TW bands below which the wobbling energy increases and above which it decreases with spin. The nucleus ^{183}Au is, so far, the only nucleus in which both the increasing and the decreasing parts are observed and thus gives the experimental evidence of the complete transverse wobbling phenomenon.
ABSTRACT
Herein, we report synthesis, characterization, anti-diabetic, anti-inflammatory and anti-oxidant activities of hydroxytriazenes derived from sulpha drugs, namely sulphanilamide, sulphadiazine, sulphapyridine and sulphamethazine. Before biological screening of the compounds, theoretical prediction using PASS was done which indicates probable activities ranging from Pa (probable activity) values 65-98% for anti-inflammatory activity. As per the predication, experimental validation of some of the predicted activities particularly anti-diabetic, anti-inflammatory and anti-oxidant was done. Anti-diabetic activities have been screened using two methods namely α-amylase and α-glucosidase inhibition method and IC50 values were ranging from 66 to 260 and 148 to 401 µg/mL, while for standard drug acarbose the values were 12 µg/mL and 70 µg/mL, respectively. Docking studies have also been done for antidiabetic target pancreatic alpha amylase. The molecular docking studies in α-amylase enzyme reveal that the middle phenyl ring of all the compounds mainly occupies in the small hydrophobic pocket formed by the Ala198, Trp58, Leu162, Leu165 and Ile235 residues and sulphonamide moiety establish H-bond interaction by two water molecules. Further, anti-inflammatory activity has been evaluated using carrageenan induced paw-edema method and results indicate excellent anti-inflammatory activity by hydroxytriazenes (71 to 97%) and standard drug diclofenac 94% after 4 h of treatment. Moreover, antioxidant effect of the compounds was tested using DPPH and ABTS methods. All the compounds displayed good results (24-488 µg/mL) against ABTS radical and many compounds are more active than ascorbic acid (69 µg/mL) while all other compounds showed moderate activity against DPPH radical (292-774 µg/mL) and ascorbic acid (29 µg/mL). Thus, the studies reveal potential of sulfa drug based hydroxytriazenes as candidates for antidiabetic, anti-inflammatory and antioxidant activities which have been experimentally validated.
Subject(s)
Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Hypoglycemic Agents/chemistry , Triazenes/chemistry , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Antioxidants/chemical synthesis , Antioxidants/pharmacology , Chemistry Techniques, Synthetic , Female , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Humans , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacology , Male , Molecular Docking Simulation , Rats , Sulfadiazine/analogs & derivatives , Sulfadiazine/chemical synthesis , Sulfadiazine/pharmacology , Sulfanilamide/analogs & derivatives , Sulfanilamide/chemical synthesis , Sulfanilamide/pharmacology , Sulfapyridine/analogs & derivatives , Sulfapyridine/chemical synthesis , Sulfapyridine/pharmacology , Triazenes/chemical synthesis , Triazenes/pharmacologyABSTRACT
AIM: To investigate factors that could impact on recanalisation and reperfusion in patients undergoing mechanical thrombectomy and to assess the technical success over time. MATERIALS AND METHODS: Two hundred consecutive patients who underwent thrombectomy for a proximal anterior circulation occlusion were dichotomised into equal groups (groups 1 and 2) based on the date that immediate access to emergency general anaesthesia (GA) commenced. RESULTS: Recanalisation success using thrombolysis in cerebral infarction (TICI) 2b/3 or TICI 2c/3 significantly improved in group 2 (67% versus 93%, p<0.0001; 52% versus 78%, p=0.0002). Symptomatic haemorrhage also reduced from 9% to 4%. Despite similar presentation Alberta Stroke Program Early (computed tomography) CT Scores (ASPECTS), post-procedural ASPECTS was significantly increased in group 2 (7; [interquartile range {IQR} 4-9] versus 8 [IQR 7-9]; p=0.0034). The number of patients with a post procedural ASPECTS of 8-10 increased (46% versus 64%, p=0.0155) and the difference in ASPECTS between pre- and post-thrombectomy CT was significantly lower (2 [IQR 1-4] versus 1 [IQR 0-2], p<0.0001). GA use increased from 8% to 56% (p=0.0001) as did use of distal aspiration (59% versus 87%, p=0.0001) mostly in combination with a stent-retriever. Failed access fell from 8% to 3%. When GA was used, successful recanalisation (TICI 2b/3) was achieved more frequently (90.5% versus 76.7%; OR 3.04, 1.2-7.69, p=0.0187). CONCLUSION: Technical results for thrombectomy are improving over time. Technique modification, operator experience, and judicious use of GA may be contributing.
Subject(s)
Stroke/surgery , Thrombectomy/methods , Aged , Anesthesia/statistics & numerical data , Blood Loss, Surgical/statistics & numerical data , Cerebral Infarction/surgery , Cerebral Revascularization/methods , Cerebral Revascularization/statistics & numerical data , Female , Humans , Male , Operative Time , Prospective Studies , Thrombectomy/statistics & numerical data , Thrombolytic Therapy/methods , Thrombolytic Therapy/statistics & numerical data , Treatment OutcomeABSTRACT
AIM: Potassium (K) is one of the three major nutrients required of plant growth and muriate of potash (MoP) is the only recognized chemical fertilizer used in agriculture. In many countries, 100% of the applied MoP is imported costing huge revenue. Application of suitable potassium-solubilizing bacteria (KSB) as biofertilizer could be an integral part of K management in arable soil. The object of this study was to evaluate K-solubilizing ability of a ubiquitous micro-organism as KSB to supplement K in soil. METHODS AND RESULTS: Strain (O-5) was isolated from tea-growing soil and identified as Bacillus pseudomycoides. Phylogenetic analysis revealed that the nearest neighbours of B. pseudomycoides strain O-5 were Bacillus cereus, Bacillus thuringiensis and Bacillus toyonensis. Though the species was first identified in 1998 and is ubiquitous in soil, the role of this group of micro-organisms in nutrient cycling in soil has not been studied before. Strain solubilized 33·32 ± 2·40 µg K ml-1 in mica waste (MW; muscovite type mineral)-amended broth after 7 days incubation at 30 ± 1°C. In a soil microcosm study under laboratory condition, B. pseudomycoides strain O-5 increased K availability by 47·0 ± 7·1 mg kg-1 after 105 days incubation, while the strain released 104·9 ± 15·3 mg K kg-1 in MW-treated soil. In this study, application of isolated B. pseudomycoides with MW significantly increased K availability in soil, and that in turn facilitated K uptake by tea plants. CONCLUSION: Based on the data, it could be inferred that B. pseudomycoides could mobilize K from bound form in soil and can be utilized as K-solubilizing biofertilizer especially in combination with MW for supplementing K in soil. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus pseudomycoides strain O-5 has potential to be used as K-solubilizing biofertilizer in agriculture.
Subject(s)
Aluminum Silicates/metabolism , Bacillus/metabolism , Camellia sinensis/metabolism , Potassium/metabolism , Agriculture , Aluminum Silicates/analysis , Bacillus/classification , Bacillus/genetics , Bacillus/isolation & purification , Camellia sinensis/growth & development , Fertilizers/analysis , India , Phylogeny , Soil/chemistry , Soil Microbiology , TeaABSTRACT
Advances in imaging technologies, such as computed tomography (CT) and surface scanning, have facilitated the rapid generation of large datasets of high-resolution three-dimensional (3D) specimen reconstructions in recent years. The wealth of phenotypic information available from these datasets has the potential to inform our understanding of morphological variation and evolution. However, the ever-increasing ease of compiling 3D datasets has created an urgent need for sophisticated methods of capturing high-density shape data that reflect the biological complexity in form. Landmarks often do not take full advantage of the rich shape information available from high-resolution 3D specimen reconstructions, as they are typically restricted to sutures or processes that can be reliably identified across specimens and exclude most of the surface morphology. The development of sliding and surface semilandmark techniques has greatly enhanced the quantification of shape, but their application to diverse datasets can be challenging, especially when dealing with the variable absence of some regions within a structure. Using comprehensive 3D datasets of crania that span the entire clades of birds, squamates and caecilians, we demonstrate methods for capturing morphology across incredibly diverse shapes. We detail many of the difficulties associated with applying semilandmarks to comparable regions across highly disparate structures, and provide solutions to some of these challenges, while considering the consequences of decisions one makes in applying these approaches. Finally, we analyze the benefits of high-density sliding semilandmark approaches over landmark-only studies for capturing shape across diverse organisms and discuss the promise of these approaches for the study of organismal form.
Um guia prático para demarcação de semi pontos de referência de superfície e de deslizamento em análises morfométricas Os avanços nas tecnologias de imagem, como a tomografia computadorizada (CT) e a varredura de superfície, facilitaram a rápida geração de grandes conjuntos de dados de reconstruções de espécimes 3D de alta resolução nos últimos anos. A riqueza de informações fenotípicas disponíveis nesses conjuntos de dados tem o potencial de informar nossa compreensão da variação e evolução morfológica. No entanto, a facilidade cada vez maior de compilar conjuntos de dados 3D criou uma necessidade urgente de métodos sofisticados para a captura de dados de alta densidade que reflitam a complexidade biológica na forma. Os pontos de referência morfológicos geralmente não capturam o máximo das informações sobre a morfologia disponíveis nas reconstruções de espécimes 3D em alta resolução, pois normalmente são restritas a suturas ou processos que podem ser identificados de forma confiável em diferentes espécimes, excluindo a maior parte da morfologia de superfície. O desenvolvimento de técnicas de deslizamento e de semi pontos de referência de superfíce melhorou muito a quantificação da forma, mas sua aplicação a diversos conjuntos de dados pode ser um desafio, especialmente quando algumas regiões dentro de uma estrutura são ausentes. Usando conjuntos de dados tridimensionais abrangentes do crânio, abrangendo todos os clados de pássaros, lagartos Squamata e cecílias, nós demonstramos métodos para captura da morfologia em formas incrivelmente diversas. Nós detalhamos muitas das dificuldades associadas à aplicação de semi pontos de referência em regiões comparáveis de estruturas altamente díspares, e fornecemos soluções para alguns desses desafios, enquanto consideramos as consequências das decisões tomadas na aplicação dessas abordagens. Finalmente, analisamos os benefícios das abordagens de deslizamento do semi pontos de referência em alta densidade para capturar a forma em diversos organismos e discutir a promessa dessas abordagens para o estudo da forma do organismo. Translated to Portuguese by Diego Vaz (dbistonvaz@vims.edu).
ABSTRACT
Exclusive measurements of the quasifree ppâppπ^{+}π^{-} reaction have been carried out at WASA@COSY by means of pd collisions at T_{p}=1.2 GeV. Total and differential cross sections have been extracted covering the energy region T_{p}=1.08-1.36 GeV, which is the region of N^{*}(1440) and Δ(1232)Δ(1232) resonance excitations. Calculations describing these excitations by t-channel meson exchange are at variance with the measured differential cross sections and underpredict substantially the experimental total cross section. An isotensor ΔN dibaryon resonance with I(J^{P})=2(1^{+}) produced associatedly with a pion is able to overcome these deficiencies.
ABSTRACT
Slow-slip events are earthquake-like events only with much lower slip rates. While peak coseismic velocities can reach tens of meters per second, slow-slip is on the order of 10-7±2 m/s and may last for days to weeks. Under the rate-and-state model of fault friction, slow-slip is produced only when the asperity size is commensurate with the critical nucleation size, a function of frictional properties. However, it is unlikely that all subduction zones embody the same frictional properties. In addition to friction, plastic flow of antigorite-rich serpentinite may significantly influence the dynamics of fault slip near the mantle wedge corner. Here, we show that the range of frictional parameters that generate slow slip is widened in the presence of a serpentinized layer along the subduction plate interface. We observe increased stability and damping of fast ruptures in a semi-brittle fault zone governed by both brittle and viscoelastic constitutive response. The rate of viscous serpentinite flow, governed by dislocation creep, is enhanced by high ambient temperatures. When effective viscosity is taken to be dynamic, long-term slow slip events spontaneously emerge. Integration of rheology, thermal effects, and other microphysical processes with rate-and-state friction may yield further insight into the phenomenology of slow slip.
ABSTRACT
AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non-neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis-associated speck-like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are early events in ALS, we hypothesized that PRRs might be abnormally expressed in muscle fibre degeneration. METHODS: Western blot analysis, real-time PCR and immunohistochemistry were performed with muscle tissue from presymptomatic and early-symptomatic male SOD1(G93A) mice and with muscle biopsies of control and sporadic ALS (sALS) patients. Analysed PRRs include nucleotide-binding oligomerization domain-like (NOD-like) receptor protein 1 (NLRP1), NLR protein 3 (NLRP3), NLR family CARD domain-containing 4 (NLRC4) and absent in melanoma 2. Additionally, expression levels of ASC, caspase 1, interleukin 1 beta (IL1ß) and interleukin 18 (IL18) were evaluated. RESULTS: Expression of PRRs and ASC was detected in murine and human tissue. The PRR NLRC4, caspase 1 and IL1ß were significantly elevated in denervated muscle of SOD1(G93A) mice and sALS patients. Furthermore, levels of caspase 1 and IL1ß were already increased in presymptomatic animals. CONCLUSION: Our findings suggest that increased inflammasome activation may be involved in skeletal muscle pathology in ALS. Furthermore, elevated levels of NLRC4, caspase 1 and IL1ß reflect early changes in the skeletal muscle and may contribute to the denervation process.
Subject(s)
Amyotrophic Lateral Sclerosis/metabolism , Inflammasomes/metabolism , Muscle, Skeletal/metabolism , Receptors, Pattern Recognition/metabolism , Amyotrophic Lateral Sclerosis/pathology , Animals , Humans , Mice , Muscle, Skeletal/pathology , Superoxide Dismutase-1/metabolismABSTRACT
Taking advantage of the high acceptance and axial symmetry of the WASA-at-COSY detector, and the high polarization degree of the proton beam of COSY, the reaction p[over â]pâppη has been measured close to threshold to explore the analyzing power A_{y}. The angular distribution of A_{y} is determined with the precision improved by more than 1 order of magnitude with respect to previous results, allowing a first accurate comparison with theoretical predictions. The determined analyzing power is consistent with zero for an excess energy of Q=15 MeV, signaling s-wave production with no evidence for higher partial waves. At Q=72 MeV the data reveal strong interference of Ps and Pp partial waves and cancellation of (Pp)^{2} and Ss^{*}Sd contributions. These results rule out the presently available theoretical predictions for the production mechanism of the η meson.
ABSTRACT
The ion-exchange kinetics of a tracer ion (Cs+ and Ba2+) in presence of a bulk ion (Na+/H+) has been measured in Nafion-117 membrane for a range of concentrations of NaCl/HNO3 using the nonstationary radiotracer method. A systematic increase in the ion-exchange rate and decrease in the partition coefficients of the tracer ions between membrane and solution have been observed with the increase in bulk ion concentration. The sigmoidal nature of experimental profiles indicates film-diffusion-controlled kinetics even for well-stirred solutions. In the absence of an existing analytical or numerical solution, a simple empirical approach has been proposed to find the variable membrane surface concentration and has been used to solve the membrane diffusion equation by the finite difference method. The fitting of the experimental curves with a single diffusion coefficient for Cs+/Ba2+ has been achieved. The exchange rate has been found to be independent of the stirring speed beyond a limiting speed.
ABSTRACT
The double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT. The molecular dynamics studies identified important interactions, which may be responsible for the AKT inhibition and efficacy of 3-AWA towards AKT binding pocket. Interestingly, the p21 deceleration was rescued by incubating the cells with 3-AWA in the presence of an ER stress inhibitor, Salubrinal. Furthermore, we demonstrated that p21 expression decreases solitarily in Par-4+/+ MEFs; albeit, ER stress-induced JNK activation was observed in both Par-4+/+ and Par-4-/- MEFs. Par-4 knockdown or overexpression studies established that ectopic Par-4 along with ER stress are not sufficient to downregulate p21 in PC-3 cells but are adequate for DU-145 cells and that the ER stress inflicted activation of JNK, inhibition of AKT and Par-4 induction are all crucial to p21 downmodulation by 3-AWA. By using isogenic cell lines, such as HCT-116 p53+/+ and HCT-116 p53-/-, we found that deceleration in p21 expression due to ER stress is p53 independent. Moreover, in orthotopic carcinogen-induced rat colorectal carcinoma model, we found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil.
ABSTRACT
AIM: The aim of this study was to determine the prevalence of gastrointestinal (GI) parasitic infections in goats of hilly region of Meghalaya. MATERIALS AND METHODS: A total of 834 fecal samples of goats were screened for 1 year (2014-2015) using flotation techniques. RESULTS: The overall prevalence of GI parasitic infections in goats was 28.65%. Season-wise highest infections were recorded during rainy season (34.92%) followed by cool (26.87%), hot (26.62%), and cold (20.39%) seasons. Helminths and protozoa infections were recorded in 63.60% and 23.02% animals, respectively. Among the helminths, Strongyle spp. (32.63%) was recorded highest followed by Trichuris spp. (12.55%), Moniezia spp. (10.04%), and Trichuris spp. (8.36%). Among protozoa, only Eimeria spp. was detected. Seven different species of Eimeria spp. were identified, viz., Eimeria christenseni, Eimeria hirci, Eimeria caprina, Eimeria jolchijevi, Eimeria ninakohlyakimovae, Eimeria arloingi, and Eimeria kocharii for the first time from Meghalaya. Maximum egg per gram and oocyst per gram of feces were recorded in the month of August (932.4) and September (674.05), respectively. Mixed infections were recorded in 13.38% samples. Coproculture of goat fecal samples revealed the presence of Haemonchus contortus (72.16%), Oesophagostomum spp. (14.41%), Strongyloides spp. (8.91%), and Trichostrongylus spp. (4.50%) larvae. CONCLUSION: This study indicates that GI helminths and protozoa infections are prevalent in goats of this hilly region of Meghalaya, throughout the year and highly prevalent during rainy season.
ABSTRACT
Isotopic composition of dilute Pu solutions (1-3900µg/mL) has been determined by analysis of HPGe detector response function in the 90-105keV region of gamma ray spectra. Results are in excellent agreement with that obtained from mass spectrometric measurements. The present method has been successfully applied for samples of low Pu concentrations, which otherwise is not possible using the conventional 120-415keV region of plutonium γ ray spectra.
ABSTRACT
Alpha-motoneurons and muscle fibres are structurally and functionally interdependent. Both cell types particularly rely on endoplasmic reticulum (ER/SR) functions. Mutations of the ER proteins VAPB, SigR1 and HSP27 lead to hereditary motor neuron diseases (MNDs). Here, we determined the expression profile and localization of these ER proteins/chaperons by immunohistochemistry and immunoblotting in biopsy and autopsy muscle tissue of patients with amyotrophic lateral sclerosis (ALS) and other neurogenic muscular atrophies (NMAs) and compared these patterns to mouse models of neurogenic muscular atrophy. Postsynaptic neuromuscular junction staining for VAPB was intense in normal human and mouse muscle and decreased in denervated Nmd2J mouse muscle fibres. In contrast, VAPB levels together with other chaperones and autophagy markers were increased in extrasynaptic regions of denervated muscle fibres of patients with MNDs and other NMAs, especially at sites of focal myofibrillar disintegration (targets). These findings did not differ between NMAs due to ALS and other causes. G93A-SOD1 mouse muscle fibres showed a similar pattern of protein level increases in denervated muscle fibres. In addition, they showed globular VAPB-immunoreactive structures together with misfolded SOD1 protein accumulations, suggesting a primary myopathic change. Our findings indicate that altered expression and localization of these ER proteins and autophagy markers are part of the dynamic response of muscle fibres to denervation. The ER is particularly prominent and vulnerable in both muscle fibres and alpha-motoneurons. Thus, ER pathology could contribute to the selective build-up of degenerative changes in the neuromuscular axis in MNDs.
Subject(s)
Membrane Proteins/metabolism , Membrane Proteins/physiology , Motor Neuron Disease/pathology , Amyotrophic Lateral Sclerosis/physiopathology , Animals , Autopsy , Disease Models, Animal , Endoplasmic Reticulum/pathology , Humans , Immunohistochemistry , Mice , Mice, Transgenic , Motor Neurons/metabolism , Muscle Denervation , Muscle, Skeletal/pathology , Neuromuscular Junction , Spinal Cord/pathology , Superoxide Dismutase/metabolism , Superoxide Dismutase-1/metabolism , Vesicular Transport Proteins/physiologyABSTRACT
The incitement of unfolded protein response (UPR) during endoplasmic reticulum (ER) stress by diverse intracellular (hypoxia, nutrient deprivation, etc.) or extracellular (environmental or drug induced) stimuli is considered a major threat for perturbing cellular homeostasis leading to the aggregation of unfolded proteins inside the cell. The catastrophic UPR events emerge as a prime cellular adaptation by remodeling cancer cell signaling and restoring ER homeostasis in favor of tumor growth. The transient ER stress protects cancer cells from undergoing apoptosis, whereas the prolonged stress response further activates many cell death pathways. The present review summarizes the UPR mediated triggering of transcriptional and translational reprogramming, which will provide novel therapeutic strategies towards pro-death mechanisms rather than a cellular adaptation in tumorigenesis. Nonetheless, the current topic also points out the reprogramming of emerging molecular switching events by complex UPR-mediated signaling to trigger apoptosis. The novel agents from various natural, semi-synthetic and synthetic sources that target ER stress signaling pathway to modulate selectively the UPR phenomena with preclinical efficacy are outlined. Since major emphasis on ER stress-induced transcriptional and translational reprogramming remains to be explored, we believe that the current subject will instigate more attention from the biomedical researchers in this certain research direction.