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.

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.

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.

Review of the bioenvironmental methods for malaria control with special reference to the use of larvivorous fishes and composite fish culture in central Gujarat, India.

Mosquito control with the use of insecticides is faced with the challenges of insecticide resistance in disease vectors, community refusal, their high cost, operational difficulties, and environmental concern. In view of this, integrated vector control strategies with the use of larvivorous fishes such as Guppy (Poecilia reticulata) and Gambusia (G. affinis) as biological control agents were used in controlling mosquito breeding in different types of breeding places such as intradomestic containers, various types of wells, rice-fields, pools, ponds and elsewhere in malaria prone rural areas of central Gujarat. Attempts were also made to demonstrate composite fish culture in unused abandoned village ponds by culturing Guppy along with the food fishes such as Rohu (Labeo rohita), Catla (Catla catla) and Mrigal (Cirrhinus mrigala). Income generated from these ponds through sale of fishes was utilized for mosquito control and village development. The technology was later adopted by the villagers themselves and food fish culture was practised in 23 ponds which generated an income of Rs 1,02,50,992 between 1985 and 2008. The number of villages increased from 13 to 23 in 2008 and there was also gradual increase of income from Rs 3,66,245 in 1985-90 to Rs 55,06,127 in 2002-08 block. It is concluded that larvivorous fishes can be useful tool in controlling mosquito breeding in certain situations and their use along with composite fish culture may also generate income to make the programme self-sustainable.

Atmospheric aerosols at a regional background Himalayan site--Mukteshwar, India.

Continuous aerosol measurements were made at a regional background station (Mukteshwar) located in a rural Himalayan mountain terrain from December 2005 to December 2008 for a period of 3 years. The average concentrations of particulate matter less than or equal to 10 µm (PM10), particulate matter less than or equal to 2.5 µm (PM2.5) and black carbon (BC) are 46.0, 26.6 and 0.85 µg/m(3) during the study period. Majority of the PM10 values lie below 100 µg/m(3) while majority of the PM2.5 values lie below 30 µg/m(3). It is further seen that during the monsoon months, especially July and August, the average values are comparatively low. It is also noted that the PM2.5/PM10 ratios between 0.50 and 0.75 have the maximum frequency distribution in the data set. Furthermore, the monthly mean ratio of BC to PM2.5 mass lies between 3.0 and 7.5 % during the study period. Though the average PM10 and PM2.5 concentrations during the study period are less than the respective Indian ambient air quality standards, however, they are still above the WHO guidelines and would have adverse health impacts. This shows that even in rural/background regions that are far away from major pollution sources or urban areas, the aerosol concentrations are significant and require long-term monitoring, source quantification and aerosol model simulations.

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.

Battling malaria iceberg incorporating strategic reforms in achieving Millennium Development Goals & malaria elimination in India.

Malaria control in India has occupied high priority in health sector consuming major resources of the Central and State governments. Several new initiatives were launched from time to time supported by foreign aids but malaria situation has remained static and worsened in years of good rainfall. At times malaria relented temporarily but returned with vengeance at the local, regional and national level, becoming more resilient by acquiring resistance in the vectors and the parasites. National developments to improve the economy, without health impact assessment, have had adverse consequences by providing enormous breeding grounds for the vectors that have become refractory to interventions. As a result, malaria prospers and its control is in dilemma, as finding additional resources is becoming difficult with the ongoing financial crisis. Endemic countries must contribute to make up the needed resources, if malaria is to be contained. Malaria control requires long term planning, one that will reduce receptivity and vulnerability, and uninterrupted financial support for sustained interventions. While this seems to be a far cry, the environment is becoming more receptive for vectors, and epidemics visit the country diverting major resources in their containment, e.g. malaria, dengue and dengue haemorrhagic fevers, and Chikungunya virus infection. In the last six decades malaria has taken deep roots and diversified into various ecotypes, the control of these ecotypes requires local knowledge about the vectors and the parasites. In this review we outline the historical account of malaria and methods of control that have lifted the national economy in many countries. While battles against malaria should continue at the local level, there is a need for large scale environmental improvement. Global Fund for AIDS, Tuberculosis and Malaria has provided huge funds for malaria control worldwide touching US$ 2 billion in 2011. Unfortunately it is likely to decline to US$ 1.5 billion in the coming years against the annual requirement of US$ 5 billion. While appreciating the foreign assistance, we wish to highlight the fact that unless we have internal strength of resources and manpower, sustained battles against malaria may face serious problems in achieving the final goal of malaria elimination.

Meaningful task-specific training (MTST) for stroke rehabilitation: a randomized controlled trial.

BACKGROUND/OBJECTIVE: The upper extremity motor deficit is one of the functional challenges in post stroke patients. The objective of the present study was to evaluate the effectiveness of the meaningful task-specific training (MTST) on the upper extremity motor recovery during the subacute phase after a stroke. METHOD: This was a randomized, controlled, double-blinded trial in the neurology department of a university hospital and occupational therapy unit of a rehabilitation institute. A convenience sample of 103 people, 4 to 24 weeks (mean, 12.15 weeks) after the stroke, was randomized into 2 groups (MTST, 51; standard training group, 52). Subjects in the Brunnstrom stage of arm recovery of 2 to 5 were included in the study. Ninety-five participants completed the 8-week follow-up. INTERVENTIONS: Participants were assigned to receive either the MTST or dose-matched standard training program based on the Brunnstrom stage and Bobath neurodevelopmental technique, 4 to 5 days a week for 4 weeks. Fugl-Meyer assessment (FMA), Action Research Arm Test (ARAT), Graded Wolf Motor Function Test (GWMFT), and Motor Activity Log (MAL) were outcome measures RESULTS: The MTST group showed a positive improvement in the mean scores on the outcome measures at post and follow-up assessments in comparison to the control group. Further, statistically significant differences were observed in changes between the groups at post and follow-up assessment for FMA, ARAT, GWMFT, and MAL. CONCLUSION: The MTST produced statistically significant and clinically relevant improvements in the upper extremity motor recovery of the patients who had a subacute stroke.

Application of ethyl chloroformate derivatization for solid-phase microextraction-gas chromatography-mass spectrometric determination of bisphenol-A in water and milk samples.

A simple and rapid analytical method based on in-matrix ethyl chloroformate (ECF) derivatization has been developed for the quantitative determination of bisphenol-A (BPA) in milk and water samples. The samples containing BPA were derivatised with ECF in the presence of pyridine for 20 s at room temperature, and the non-polar derivative thus formed was extracted using polydimethylsiloxane solid-phase microextraction (SPME) fibres with thicknesses of 100 µm followed by analysis using gas chromatography-mass spectrometry. Three alkyl chloroformates (methyl, ethyl and isobutyl chloroformate) were tested for optimum derivatisation yields, and ECF has been found to be optimum for the derivatisation of BPA. Several parameters such as amount of ECF, pyridine and reaction time as well as SPME parameters were studied and optimised in the present work. The limit of detection for BPA in milk and water samples was found to be 0.1 and 0.01 µg L(-1), respectively, with a signal-to-noise ratio of 3:1. The limit of quantitation for BPA in milk and water was found to be 0.38 and 0.052 µg L(-1), respectively, with a signal-to-noise ratio of 10:1. In conclusion, the method developed was found to be rapid, reliable and cost-effective in comparison to silylation and highly suitable for the routine analysis of BPA by various food and environmental laboratories.

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.

Timing of myofunctional appliance therapy.

OBJECTIVE: To identify the stage of skeletal maturity, as depicted by the Cervical Vertebrae Maturity Index at which the maximal response to myofunctional therapy could be expected. DESIGN: The soft copies of pre and post treatment lateral cephalometric radiographs of the sample comprising of 48 subjects, on myofunctional therapy, were traced on 'Nemotec Dental Studio NX'software. Three groups were formed based on the stages of skeletal maturity and comparison was done. RESULTS: The treated samples were compared with control samples consisting of subjects with untreated Class II malocclusions, also selected on the basis of stages in cervical vertebrae maturation. Inter-group comparison of the treated samples revealed statistically significant changes in Group II (Stages 3 to 4 of Cervical Vertebrae Maturity Index). CONCLUSION: Maximum response to myofunctional therapy can be expected in patients during the stages 3 to 4 of cervical vertebrae maturation index, i.e., during or slightly after the pubertal peak.

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.

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.

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.

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.

Larvivorous fish in wells target the malaria vector sibling species of the Anopheles culicifacies complex in villages in Karnataka, India.

Malaria was a major problem in a sericulture area of Karnataka, south India, where Anopheles culicifacies s.l. and A. fluviatilis s.l. were considered to be the main vectors. Sibling species complexes of these two species were analysed in three ecologically different villages. Among A. culicifacies, only sibling species A and B were found. In Puram, a village with 22 wells, species A predominated; species B predominated in a village with four wells and a stream, and in a village with a stream and no wells. Poecilia reticulata fish were introduced into all wells and streams in the villages, and after one year no vectors were found in Puram, and all, or nearly all, A. culicifacies were species B in the other two villages. All A. fluviatilis belonged to the sibling species T. Blood meal analysis indicated that a few of the A. culicifacies collected had fed on humans while all the A. fluviatilis had fed on bovines. Before the introduction of fish, the annual parasite incidence for malaria was high in Puram, but much lower in the other two villages. From 1998 (over one year after release of fish) until 2003, no malaria cases were detected in the three villages.

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.