Assessment of carbonaceous aerosols at Mukteshwar: A high-altitude (~2200 m amsl) background site in the foothills of the Central Himalayas.

The present study examined the equivalent black carbon (eBC) mass concentrations measured over 10.5 years (September 2005-March 2016) using a 7-wavelength Aethalometer (AE-31) at Mukteshwar, a high-altitude and regional background site in the foothills of Indian central Himalayas. The total spectral absorption coefficient (babs) was divided into three categories: black carbon (BC) and brown carbon (BrC); fossil fuels (FF) and wood/biomass burning (WB/BB); and primary and secondary sources. At the wavelength of 370 nm, a significant BrC contribution (25 %) to the total babs is identified, characterized by a pronounced seasonal variation with winter (December-January-February) maxima (31 %) and post-monsoon (October and November) minima (20 %); whereas, at 660 nm, the contribution of BrC is dramatically less (9 %). Climatologically, the estimated BCFF at 880 nm ranges from 0.25 ± 0.19 µg m-3 in July to 1.17 ± 0.80 µg m-3 in May with the annual average of 0.67 ± 0.63 µg m-3, accounting for 79 % of the BC mass. The maximum BCFF/BC fraction reaches its peak value during the monsoon (July and August, 85 %), indicating the dominance of local traffic emissions due to tourism activities. Further, the highest BCWB concentration observed during pre-monsoon (March-May) suggests the influence of local forest fires along with long-range transported aerosols from the low-altitude plains. The increased contribution of BrC (26 % at 370 nm) and WB absorption (61 % at 370 nm) to the total absorption at the shorter wavelengths suggests that wood burning is one of the major sources of BrC emissions. Secondary BrC absorption accounts for 24 % [91 %] of the total absorption [BrC absorption] at 370 nm, implying the dominance of secondary sources in BrC formation. A trend analysis for the measured BC concentration shows a statistically significant increasing trend with a slope of 0.02 µgm-3/year with a total increase of about 22 % over the study period. A back trajectory-based receptor model, potential source contribution function (PSCF), was used to identify the potential regional source region of BC. The main source regions of BC are the northwest states of India in the IGP region and the northeast Pakistan region.

De novo genome sequencing of mycoparasite Mycogone perniciosa strain MgR1 sheds new light on its biological complexity.

Mycogone perniciosa is a mycoparasite causing Wet Bubble Diseases (WBD) of Agaricus bisporus. In the present study, the whole genome of M. perniciosa strain MgR1 was sequenced using Illumina NextSeq500 platform. This sequencing generated 8.03 Gb of high-quality data and a draft genome of 39 Mb was obtained through a de novo assembly of the high-quality reads. The draft genome resulted into prediction of 9276 genes from the 1597 scaffolds. NCBI-based homology analysis revealed the identification of 8660 genes. Notably, non-redundant protein database analysis of the M. perniciosa strain MgR1 revealed its close relation with the Trichoderma arundinaceum. Moreover, ITS-based phylogenetic analysis showed the highest similarity of M. perniciosa strain MgR1 with Hypomyces perniciosus strain CBS 322.22 and Mycogone perniciosa strain PPRI 5784. Annotation of the 3917 genes of M. perniciosa strain MgR1 grouped in three major categories viz. biological process (2583 genes), cellular component (2013 genes), and molecular function (2919 genes). UniGene analysis identified 2967 unique genes in M. perniciosa strain MgR1. In addition, prediction of the secretory and pathogenicity-related genes based on the fungal database indicates that 1512 genes (16% of predicted genes) encode for secretory proteins. Moreover, out of 9276 genes, 1296 genes were identified as pathogenesis-related proteins matching with 51 fungal and bacterial genera. Overall, the key pathogenic genes such as lysine M protein domain genes, G protein, hydrophobins, and cytochrome P450 were also observed. The draft genome of MgR1 provides an understanding of pathogenesis of WBD in A. bisporus and could be utilized to develop novel management strategies.

Nutritional and Biochemical Characterization of Panus lecomtei Mushroom (Agaricomycetes) from India and Its Cultivation.

Panus lecomtei is emerging as an edible mushroom found worldwide and particularly in the Northern Hemisphere. The mushroom contains a substantial amount of useful nutritional and medicinal compounds. In the present study, we have examined a specimen of P. lecomtei submitted to the ICAR-Directorate of Mushroom Research gene bank. The specimen was examined for taxonomical characters using classical and molecular tools. Attempts were made for cultivation of this mushroom under controlled conditions using sawdust-based substrate. The specimen was characterized by its purplish fruiting body having coarse, rigid, dense hairs on the cap, pubescent stipe, and abundant metuloids. Molecular identification through conserved ITS region was done and the sequence was deposited in NCBI GenBank under accession number MN332200. Nutritional profiling and biochemical analysis showed that the mushroom contained high carbohydrate but low fat contents. The mushroom showed the presence of phenolics, ß-carotene, and lycopene. The analysis also showed substantial antioxidant properties in the mushroom. The findings presented herein point out that P. lecomtei can be used as a potential edible mushroom for diversification of mushroom production in India.

Genetic improvement in Pleurotus (oyster mushroom): a review.

Pleurotus is an important genus comprising several edible species of great commercial significance. These species are grown all across the world. The production areas of Pleurotus mainly belong to the Asian part and are gaining wide popularity across the globe owing to their promising nutritional gains. The demand for improved strains with high productivity has also been rising. The genetic improvement in Pleurotus started with a simple selection technique, which later utilized hybridization (intraspecific, interspecific and intergeneric) and mutation breeding. The traits such as productivity, sporelessness and quality improvement are important objectives on which most of the works have been done so far. However, new generation approaches such as molecular breeding, genetic transformation and genome editing techniques also added pace to the present improvement process. Hitherto, seven species of Pleurotus have been sequenced and a sizable data has been generated that can be used in further breeding programs. This paper discusses and summarizes various research findings on genetic improvement of Pleurotus and gives an outlook for future breeding programs.

Measurement of pH and calcium ions release from different calcium hydroxide pastes at different intervals of time: Atomic spectrophotometric analysis.

AIM: To evaluate the effect of different vehicles on pH and release of calcium ions from calcium hydroxide (CH) paste from apical third of root canals. METHODS: 40 single rooted extracted human mandibular premolars were instrumented with RevoS files (MicroMega) up to ISO size 40. The teeth were divided into 4 groups on the basis of vehicle as follows: Group I - calcium hydroxide mixed with 2% chlorhexidine; Group II - calcium hydroxide mixed with propylene glycol; Group III - calcium hydroxide mixed with glycerine; and Control - calcium hydroxide mixed with double distilled water. Each group had two subgroups (n = 5) on the basis of the calcium hydroxide delivery. Subgroup A - calcium hydroxide paste placed with spiral filler (Lentulospiral) subgroup B - calcium hydroxide paste placed with flat wire filler (Paste Inject). pH and calcium ion release was evaluated at 24 h, 48 h, 7th day, 15th day and 30th day using a pH meter and atomic absorption spectrophotometer respectively. RESULTS: The calcium release from various groups was highest for CH+glycerine (Group III) followed by CH+chlorhexidine (Group I), CH+propylene glycol (Group II) and CH+double distilled water (control). At all the intervals the differences in calcium ion release among the groups were statistically significant (p < 0.05), except on day 7. Delivery technique did not have a significant effect on calcium ion release. Highest pH values were recorded from CH+glycerine group at day 30 for both the delivery systems, however rise in pH from day 1 to day 30 were non-significant in all groups with both delivery systems. CONCLUSION: Demonstrable changes in calcium ion release occurred from the calcium hydroxide mixed with various vehicles and CH+glycerine group showed the maximum calcium ion release at all intervals and highest pH day 30.

Determination of pesticide and phthalate residues in tea by QuEChERS method and their fate in processing.

In this study, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was applied for the analysis of the multiclass pesticide residues of 12 organochlorines (OCs), 9 organophosphates (OPs), 11 synthetic pyrethroids (SPs), 4 herbicides, 6 phthalates in raw tea (loose tea, branded tea and herbal tea), and tea infusion in 4 different containers (glass cup, earthen cup, plastic bag and disposal cup). In loose tea and branded tea residues, malathion (0.257 and 0.118 mg kg-1), cypermethrin (0.065 and 0.030 mg kg-1), and fenvalerate (0.032 and 0.030 mg kg-1) were detected, respectively. In herbal tea, residues of only cypermethrin (0.053 mg kg-1) and fenvalerate (0.045 mg kg-1) were detected. Tea infusion samples contained in a plastic bag were found to be contaminated with only dibutyl phthalate (DBP) (0.038 mg kg-1). Disposable cup was found to be contaminated with DBP (0.026 mg kg-1) and diethyl phthalate (DEP) (0.004 mg kg-1). Further, to know the processing behavior of pesticides, the spiked raw tea was subjected to tea infusion at different brewing times (2, 5, 10 min). The analysis demonstrated that dimethoate, dichlorvos, and malathion had shown more than 10 % of translocation at 5 min of brewing time. Further brewing for 10 min revealed the reduction in concentration of pesticides. Leaching of phthalate residues from different plastic containers was also studied at 10, 30, and 60 min. DBP, benzyl butyl phthalate (BzBP), and di-2-(ethylhexyl) phthalate (DEHP) were leached in the tea infusion samples packed in plastic bags. On the other hand, in disposable cups, leaching of DBP, DEP, and dimethyl phthalate were found. The concentration of phthalate residues increased with retention time. Pesticide and phthalate contaminants were recorded at low quantities in few samples only.

Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 µm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

Traumatic amputations in children and adolescents: A demographic study from a tertiary care center in Northern India.

PURPOSE: To determine the demographic pattern, level, mechanism of traumatic amputation in children and adolescent age group and to compare findings with other studies. METHODS: Patients aged less than 18 years with traumatic amputation attending Department of Physical Medicine and Rehabilitation, King George's Medical University, Lucknow, India between July 2013 and January 2016 were enrolled and their demographic characteristics were analyzed. RESULTS: Fifty-three patients were included aged less than 18 years when injured. Mean age of the population studied was 9.89 ± 4.13 with male to females ratio of 3:2. Majority (69.81%) of traumatic amputations involved lower limb. Most common level was unilateral transtibial (35.85%), followed by transfemoral (16.98%). In upper limb, most common type was transradial. RTA followed by train accidents was most common mechanism of traumatic amputation. 8 patients needed revision surgery. 52.8% patients of acquired amputations complained of phantom sensation and 37.74% phantom pain. CONCLUSIONS: This study aims to visualize the current scenario and the data generated could be possibly helpful in planning policies and programs at institutional as well as at higher levels for prevention, treatment and distribution of resource to the young amputee population, to ensure their better health care and also opportunities in life.

Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE.

Cancer invasion is a hallmark of metastasis. The mesenchymal mode of cancer cell invasion is mediated by elongated membrane protrusions driven by the assembly of branched F-actin networks. How deregulation of actin regulators promotes cancer cell invasion is still enigmatic. We report that increased expression and membrane localization of the actin regulator Lamellipodin correlate with reduced metastasis-free survival and poor prognosis in breast cancer patients. In agreement, we find that Lamellipodin depletion reduced lung metastasis in an orthotopic mouse breast cancer model. Invasive 3D cancer cell migration as well as invadopodia formation and matrix degradation was impaired upon Lamellipodin depletion. Mechanistically, we show that Lamellipodin promotes invasive 3D cancer cell migration via both actin-elongating Ena/VASP proteins and the Scar/WAVE complex, which stimulates actin branching. In contrast, Lamellipodin interaction with Scar/WAVE but not with Ena/VASP is required for random 2D cell migration. We identified a phosphorylation-dependent mechanism that regulates selective recruitment of these effectors to Lamellipodin: Abl-mediated Lamellipodin phosphorylation promotes its association with both Scar/WAVE and Ena/VASP, whereas Src-dependent phosphorylation enhances binding to Scar/WAVE but not to Ena/VASP. Through these selective, regulated interactions Lamellipodin mediates directional sensing of epidermal growth factor (EGF) gradients and invasive 3D migration of breast cancer cells. Our findings imply that increased Lamellipodin levels enhance Ena/VASP and Scar/WAVE activities at the plasma membrane to promote 3D invasion and metastasis.

Circadian variations in melatonin and cortisol in patients with cervical spinal cord injury.

PURPOSE: In cervical spinal cord injury (CSCI), afferent and efferent circuits that influence the basal production of melatonin and cortisol may be disrupted and hence disrupt the basal functions of human physiology. Therefore, the aim of this study was to assess circadian changes, if any, in serum cortisol and melatonin in patients with CSCI. METHODS: Serum levels of cortisol and melatonin were measured at 6-h intervals of the day (0600, 1200, 1800 and 0000 hours) in 22 CSCI patients, as well as 22 healthy controls. RESULTS: Significantly higher melatonin levels were observed in the patient group in morning hours, whereas a significantly lower level of melatonin was found during the night time in the patient group than in the control group. Moreover, significantly higher values were obtained in the evening and night time serum cortisol levels among the patients compared with controls. Further, when the mean values of cortisol throughout the day were tested among patient and control groups similar circadian rhythm was found. The only difference being that serum cortisol declined much more in controls in evening and night samples as compared with CSCI patients. CONCLUSION: We conclude that circadian variations exist in the circulating levels of serum cortisol and melatonin in patients with CSCI. Low levels of melatonin secretion during night may contribute to the pervasive sleep disruption and increased pain perception.

Pentazocine-induced contractures: Dilemma in management.

Pentazocine is a commonly used synthetic opioid analgesic for moderate to severe pain secondary to various conditions. Complications of parenteral opioid abuse including localized ulcerations, abscess, indurations, and sclerosis are well-documented. We present a rare case of drug abuse due to pentazocine (Fortwin) in a 32-year-old female, who had severe myogenic contractures of her knee joints.

Biology & control of Anopheles culicifacies Giles 1901.

Malaria epidemiology is complex due to multiplicity of disease vectors, sibling species complex and variations in bionomical characteristics, vast varied terrain, various ecological determinants. There are six major mosquito vector taxa in India, viz. Anopheles culicifacies, An. fluviatilis, An. stephensi, An. minimus, An. dirus and An. sundaicus. Among these, An. culicifacies is widely distributed and considered the most important vector throughout the plains and forests of India for generating bulk of malaria cases (>60% annually). Major malaria epidemics are caused by An. culicifaices. It is also the vector of tribal malaria except parts of Odisha and Northeastern States of India. An. culicifacies has been the cause of perennial malaria transmission in forests, and over the years penetrated the deforested areas of Northeast. An. culicifacies participates in malaria transmission either alone or along with An. stephensi or An. fluviatilis. The National Vector Borne Disease Control Programme (NVBDCP) spends about 80 per cent malaria control budget annually in the control of An. culicifacies, yet it remains one of the most formidable challenges in India. With recent advances in molecular biology there has been a significant added knowledge in understanding the biology, ecology, genetics and response to interventions, requiring stratification for cost-effective and sustainable malaria control. Research leading to newer interventions that are evidence-based, community oriented and sustainable would be useful in tackling the emerging challenges in malaria control. Current priority areas of research should include in-depth vector biology and control in problem pockets, preparation of malaria-risk maps for focused and selective interventions, monitoring insecticide resistance, cross-border initiative and data sharing, and coordinated control efforts for achieving transmission reduction, and control of drug-resistant malaria. The present review on An. culicifacies provides updated information on vector biology and control outlining thrust areas of research.

Profilin1 regulates invadopodium maturation in human breast cancer cells.

Invadopodia are actin-driven membrane protrusions that show oscillatory assembly and disassembly causing matrix degradation to support invasion and dissemination of cancer cells in vitro and in vivo. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas and it is been shown that its depletion enhances invasiveness and motility of breast cancer cells by increasing PI(3,4)P2 levels at the leading edge. In this study, we show for the first time that depletion of profilin1 leads to an increase in the number of mature invadopodia and these assemble and disassemble more rapidly than in control cells. Previous work by Sharma et al. (2013a), has shown that the binding of the protein Tks5 with PI(3,4)P2 confers stability to the invadopodium precursor causing it to mature into a degradation-competent structure. We found that loss of profilin1 expression increases the levels of PI(3,4)P2 at the invadopodium and as a result, enhances recruitment of the interacting adaptor Tks5. The increased PI(3,4)P2-Tks5 interaction accelerates the rate of invadopodium anchorage, maturation, and turnover. Our results indicate that profilin1 acts as a molecular regulator of the levels of PI(3,4)P2 and Tks5 recruitment in invadopodia to control the invasion efficiency of invadopodia.

Oxidative stress and antioxidative parameters in patients with spinal cord injury: implications in the pathogenesis of disease.

STUDY DESIGN: Oxygen-derived free radicals have been implicated in the pathogenesis of spinal cord injury (SCI) after trauma. OBJECTIVE: In this review we will elucidate the importance of oxidative stress and antioxidants and its possible relationship with SCI. METHODS: Literature analysis of oxidative stress, antioxidative parameters based on its implications in the pathogenesis along with devastating effect of oxidative stress parameters on SCI patients and its suggested proposed treatment by antioxidants have been performed. RESULTS: SCI remains a major health problem despite advances in neurotechnology. Previous studies have reported oxidative stress in SCI patients, but the results were inconsistent. Furthermore, increased free radical levels are reported in SCI. Moreover, we have also mentioned in this review that oxidative stress is supposed to be increased in patients with SCI, which is related to the severity of SCI pain. CONCLUSION: Oxidative stress was commonly seen in SCI patients, which may provide useful information to augment the understanding of pathophysiology of SCI patients. However, complete understanding of the biochemical events occurring at a cellular level that influence oxidative damage is required to guide future therapeutic advances. Furthermore, supplementation of antioxidants may also be considered in these patients.

Efficacy of core muscle strengthening exercise in chronic low back pain patients.

BACKGROUND AND OBJECTIVES: Low back pain is a common health problem in human being and about 5 to 15% will develop chronic low back pain (CLBP). The clinical findings of CLBP suggest that lumbar mobility is decreased and recruitment order of core muscles is altered. In literature, there is no data about the effect of core muscles strengthening in the chronicity (short duration, long duration) of CLBP. This study evaluated the effect of core muscle strengthening intervention on chronicity of chronic low back pain. METHOD: Thirty patients were recruited from the outpatient department of the National Institute for the Orthopaedically Handicapped. These 30 patients divided into two groups: A and B on the basis of duration of low back pain. Group-A patients complain about pain duration for more than twelve months and Group B complains about pain duration from three to twelve months. Both the groups were received same intervention for six weeks. Assessment was done pre intervention and post intervention after six weeks for both the groups. %For both the groups the assessment was done after six weeks for pre and post intervention. RESULTS: The result described both the groups showed improvement in all the outcome measures including pain as well as in function using Numerical pain rating scale, Oswestry Disability Index, Sorensen test, Gluteus Maximus Strength, Activation of transversus abdominis and Modified-Modified Schober's Test. The improvement was statistically non-significant with inter groups and significant within group. CONCLUSION: This study concludes that core muscle strengthening exercise along with lumbar flexibility and gluteus maximus strengthening is an effective rehabilitation technique for all chronic low back pain patients irrespective of duration (less than one year and more than one year) of their pain.

Need of Revision of Lower Limb Amputations in a North Indian Tertiary Care Centre.

INRTODUCTION: Amputation of the extremity is a big challenge to mankind. Revision rate of primary amputations stands high despite of maximum care at tertiary care centres. The purpose of this study was to establish cause for the revision, identify preventable cause and to assess outcome of revision amputation surgery. MATERIALS AND METHODS: We performed a retrospective study on lower limb revision amputations in Department of Physical Medicine and Rehabilitation and Department of Orthopaedic Surgery, King George Medical University between Jan 2012 to Jan 2015. All patients of any age group and gender admitted for revision amputation were included in the study population. RESULTS: A total of 32 patients who required revision amputation of lower limbs was included in the study, out of these 62.50 % were male and 37.50 % were female. Age of the patients ranged from 5 to 72 years with mean of 42 years. Most common level of initial amputation was below knee (56.25 %) followed by above knee amputation (31.25%). Most common indication for initial amputation was trauma (43.75%) followed by infection, vascular diseases, malignancy and leprosy. Poor stump formation was found to be most common indication for revision amputation (37.50%) followed by infection (25%), recurrent ulceration (18.75%), stitch abscess (6.25%), neuroma (6.25%), and necrosis (6.25%). All patients were treated successfully. CONCLUSION: Revision amputation increases morbidity. Poor stump formation at the time of initial amputation and infection are the most common indication for revision surgery. These are the preventable causes and every effort should be made to alleviate these as well as other preventable causes.

Mosquito-borne diseases in Assam, north-east India: current status and key challenges.

Mosquito-borne diseases, including malaria, Japanese encephalitis (JE), lymphatic filariasis and dengue, are major public health concerns in the north-eastern state of Assam, deterring equitable socioeconomic and industrial development. Among these, malaria and JE are the predominant infections and are spread across the state. The incidence of malaria is, however, gradually receding, with a consistent decline in cases over the past few years, although entry and spread of artemisinin-resistant Plasmodium falciparum remains a real threat in the country. JE, formerly endemic in upper Assam, is currently spreading fast across the state, with confirmed cases and a high case-fatality rate affecting all ages. Lymphatic filariasisis is prevalent but its distribution is confined to a few districts and disease transmission is steadily declining. Dengue has recently invaded the state, with a large concentration of cases in Guwahati city that are spreading to suburban areas. Control of these diseases requires robust disease surveillance and integrated vector management on a sustained basis, ensuring universal coverage of evidence-based key interventions based on sound epidemiological data. This paper aims to present a comprehensive review of the status of vector-borne diseases in Assam and to address the key challenges.

Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and macrophage-independent invasion in vivo.

Increased expression of HBEGF in estrogen receptor-negative breast tumors is correlated with enhanced metastasis to distant organ sites and more rapid disease recurrence upon removal of the primary tumor. Our previous work has demonstrated a paracrine loop between breast cancer cells and macrophages in which the tumor cells are capable of stimulating macrophages through the secretion of colony-stimulating factor-1 while the tumor-associated macrophages (TAMs), in turn, aid in tumor cell invasion by secreting epidermal growth factor. To determine how the autocrine expression of epidermal growth factor receptor (EGFR) ligands by carcinoma cells would affect this paracrine loop mechanism, and in particular whether tumor cell invasion depends on spatial ligand gradients generated by TAMs, we generated cell lines with increased HBEGF expression. We found that autocrine HBEGF expression enhanced in vivo intravasation and metastasis and resulted in a novel phenomenon in which macrophages were no longer required for in vivo invasion of breast cancer cells. In vitro studies revealed that expression of HBEGF enhanced invadopodium formation, thus providing a mechanism for cell autonomous invasion. The increased invadopodium formation was directly dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of signaling downstream of EGFR activation. HBEGF expression also resulted in enhanced invadopodium function via upregulation of matrix metalloprotease 2 (MMP2) and MMP9 expression levels. We conclude that high levels of HBEGF expression can short-circuit the tumor cell/macrophage paracrine invasion loop, resulting in enhanced tumor invasion that is independent of macrophage signaling.

Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation.

Most cancer patients die as a result of metastasis, thus it is important to understand the molecular mechanisms of dissemination, including intra- and extravasation. Although the mechanisms of extravasation have been vastly studied in vitro and in vivo, the process of intravasation is still unclear. Furthermore, how cells in the tumor microenvironment facilitate tumor cell intravasation is still unknown. Using high-resolution imaging, we found that macrophages enhance tumor cell intravasation upon physical contact. Macrophage and tumor cell contact induce RhoA activity in tumor cells, triggering the formation of actin-rich degradative protrusions called invadopodia, enabling tumor cells to degrade and break through matrix barriers during tumor cell transendothelial migration. Interestingly, we show that macrophage-induced invadopodium formation and tumor cell intravasation also occur in patient-derived tumor cells and in vivo models, revealing a conserved mechanism of tumor cell intravasation. Our results illustrate a novel heterotypic cell contact-mediated signaling role for RhoA, as well as yield mechanistic insight into the ability of cells within the tumor microenvironment to facilitate steps of the metastatic cascade.

Comparison of esthetic outcome after extraction or non-extraction orthodontic treatment in class II division 1 malocclusion patients.

INTRODUCTION: The extraction of premolars as a practical form of orthodontic therapy has been accepted for many years, but there remains a controversy regarding the effect of premolar extraction to improve esthetics as well as dentoskeletal relationship. The esthetic impact of the soft-tissue profile might play a major role in deciding on premolar extraction or non-extraction treatment, particularly in borderline patients. This cephalometric study was undertaken to compare the post-treatment soft-tissue profiles of successfully managed Class II, Division 1 malocclusions treated with either all first premolar extractions or treatment with a non-extraction therapy. MATERIALS AND METHODS: The sample consisted of 100 post-pubertal female patients of Class II Division I malocclusion. Group 1, treated with four first premolar extractions, consisted of 50 female patients with a mean age of 14 years 1 month. Group 2, treated without extractions, consisted of 50 patients with a mean age of 13 years 5 months. Pre-treatment and post-treatment lateral cephalometric radiographs were evaluated. The pre-treatment to post-treatment stage comparison and the intergroup comparison of the treatment changes were conducted between extraction and non-extraction groups of Class II malocclusion samples with t-tests. RESULTS: The soft-tissue facial profiles of the extraction and non-extraction samples were the same following active treatment except for a more retruded lower lip and a more pronounced lower labial sulcus in those patients subjected to extraction. CONCLUSIONS: The extraction or non-extraction decision, if based on sound diagnostic criteria, seems to have no systematic detrimental effects on the facial profile.