Antiferromagnetic half-skyrmions electrically generated and controlled at room temperature.

Topologically protected magnetic textures are promising candidates for information carriers in future memory devices, as they can be efficiently propelled at very high velocities using current-induced spin torques. These textures-nanoscale whirls in the magnetic order-include skyrmions, half-skyrmions (merons) and their antiparticles. Antiferromagnets have been shown to host versions of these textures that have high potential for terahertz dynamics, deflection-free motion and improved size scaling due to the absence of stray field. Here we show that topological spin textures, merons and antimerons, can be generated at room temperature and reversibly moved using electrical pulses in thin-film CuMnAs, a semimetallic antiferromagnet that is a testbed system for spintronic applications. The merons and antimerons are localized on 180° domain walls, and move in the direction of the current pulses. The electrical generation and manipulation of antiferromagnetic merons is a crucial step towards realizing the full potential of antiferromagnetic thin films as active components in high-density, high-speed magnetic memory devices.

Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Secondary correction of premaxilla in bilateral cleft lip and palate with lag-screw fixation.

It is not unusual for the protruding premaxilla to attain an undesirable position after cleft lip repair. Such a premaxilla may lead to considerable problems in facial aesthetics, or oral functions, or both in early childhood. These abnormal premaxillas may produce difficulties in bone grafting and orthodontic treatment in late childhood. In such cases, surgical correction of the premaxilla in childhood is justified. From 2013 to 2018, 11 children, aged 2 to 11 years, had a secondary ostectomy of their premaxilla. A new stabilisation method (developed by us) was used to provide rigid fixation to the premaxilla. The follow up period ranged from 1 - 6 years. The results were satisfactory in all except for a few minor issues in three patients. There was significant improvement in their appearance, oral functions, and most importantly in their quality of life. The need for secondary osteotomy of the premaxilla should always be weighed against its potential complications. The fixation technique described by us, though, provides rigid fixation, but may potentially be associated with a few complications if not practised carefully.

Development of dipstick enzyme linked immunosorbent assay for on-site sero-diagnosis of Japanese encephalitis in swine.

Japanese encephalitis (JE) is an important viral zoonotic disease in Asia, especially in rural and suburban areas where rice cultivation and pig farming coexist. Pigs serve as a suitable sentinel model, the surveillance of which could predict a potential JE outbreak in human population in the immediate vicinity. However, existing diagnostics like ELISA and VNT require sophisticated laboratory facilities which are more often not available in field conditions. In the present study, we aimed at developing recombinant non-structural (NS1) protein-based dipstick IgG ELISA as an on-site assay for sero-diagnosis of JE in swine. The assay was standardized by optimizing various parameters and the following conditions were found to be ideal including 1 µg of rNS1 protein in carbonate buffer per strip of nitrocellulose membrane comb; bovine serum albumin as blocking agent at 4 °C overnight; serum dilution of 1:10 and conjugate dilution of 1:5000 in skimmed milk powder. Relative diagnostic sensitivity and specificity of dipstick IgG ELISA was 100% and 92.9%, respectively. The dipstick assay was validated in three laboratories as per OIE guidelines. The storage life of dipstick was up to 7 months at 4 °C. The assay is easy to perform and the results can be interpreted with visual observation that precludes the need for absorbance reading equipment. The standardized dipstick assay was found promising for screening swine serum samples in field conditions. Timely detection of JE virus in swine will aid in predicting the outbreak in humans and thus in taking suitable preventive and control measures.

Computational analysis for the determination of deleterious nsSNPs in human MTHFR gene.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism and plays a central role in DNA methylation and biosynthesis. MTHFR mutations may alter the cellular folate supply which in turn affects nucleic acid synthesis, DNA methylation and chromosomal damage. The identification of number of SNPs in the human genome growing nowadays and hence, the evaluation of functional & structural consequences of these SNPs is very laborious by means of experimental analysis. Therefore, in the present study, recently developed various computational algorithms have been used which can predict the functional and structural consequences of the SNPs. Various computational tools like SIFT, PolyPhen2, PROVEAN, SNAP2, nsSNPAnalyzer, SNPs&GO, PhD-SNP, PMut, I-Mutant, iPTREE-STAB and MUpro were used to predict most deleterious SNPs. Additionally, ConSurf was used to find amino acids conservation and NCBI conserved domain search tool to find conserved domains in MTHFR. Post translational modification sites were predicted using ModPred. SPARKS-X was used to generate 3D structure of the native and mutant MTHFR protein, ModRefiner for further refinement, Varify3D and RAMPAGE to validate structure. Ligand binding sites were predicted using FTsite, RaptorX binding and COACH. Three SNPs i.e. R157Q, L323P and W500C predicted the most deleterious in all the tools used for functional and stability analysis. Moreover, both residues R157, L323 and W500 were predicted highly conserved, buried and structural residues by ConSurf. Post translational modification sites were also predicted at R157 and W500. The ligand binding sites were predicted at R157, L323 and W500.

Seasonal occurrence of Japanese encephalitis vectors in Bareilly district, Uttar Pradesh, India.

BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) is one of the most common causes of acute encephalitis syndrome in many states of India. Uttar Pradesh state is well known for JE endemicity, contributing 75% of total cases during recent past. Several sporadic cases have been reported from Bareilly region of the state. The disease spread by bite of Culex mosquito. Survey of literature revealed no data on mosquito fauna with reference to JE in this region. Therefore, this study was planned to survey seasonal mosquito population and occurrence of JE vectors in Bareilly region. METHODS: Mosquitoes were sampled on monthly basis from organized pig farm from February 2016 to January 2017 and identified using mosquito identification keys. The meteorological parameters of the area were obtained monthly and standard statistical methods were used to assess the relationship between different weather variables and mosquito population. RESULTS: A total of 4337 mosquitoes belonging to five genera were collected. Mosquitoes of genus Culex were predominant and contributed 84.41% to the total catch. The most dominant species was Cx. tritaeniorhynchus (30.81%), followed by Cx. quinquefasciatus (28.50%), Cx. gelidus (17.24%), Cx. pseudovishnui (11.85%), Cx. vishnui (8.11%), Cx. fuscocephala (2.70%), Cx. infula (0.76%) and Cx. bitaeniorhynchus (0.03%). Pronounced seasonal variation was observed with majority of mosquitoes showing high density in monsoon and post-monsoon period. INTERPRETATION & CONCLUSION: The present study provides knowledge on distribution of JE vector in Bareilly which indicates that the area is at risk of JE outbreak. Abundance of Culex vector clearly demarcates possible threat of JE incidence in the study area. A long-term entomological study is needed to further evaluate the significant role of different weather variables in shaping mosquito densities.

Computational analysis for the determination of deleterious nsSNPs in human MTHFD1 gene.

Single nucleotide polymorphisms (SNPs) are the most common genetic polymorphisms and play a major role in many inherited diseases. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) is one of the enzymes involved in folate metabolism. In the present study, the functional and structural consequences of nsSNPs of human MTHFD1 gene was analyzed using various computational tools like SIFT, PolyPhen2, PANTHER, PROVEAN, SNAP2, nsSNPAnalyzer, PhD-SNP, SNPs&GO, I-Mutant, MuPro, ConSurf, InterPro, NCBI Conserved Domain Search tool, ModPred, SPARKS-X, RAMPAGE, FT Site and PyMol. Out of 327 nsSNPs form human MTHFD1 gene, total 45 SNPs were predicted as functionally most significant SNPs, among which 17 were highly conserved and functional, 17 were highly conserved and structural residues. Among 45 most significant SNPs, 15 were predicted to be involved in post translational modifications. The p.Gly165Arg may interfere in homodimer interface formation. The p.Asn439Lys and p.Asp445Asn may interfere in binding interactions of MTHFD1 protein with cesium cation and potassium. The two SNPs (p.Asp562Gly and p.Gly637Cys) might interfere in interactions of MTHFD1 with ligand.

Imaging Current-Induced Switching of Antiferromagnetic Domains in CuMnAs.

The magnetic order in antiferromagnetic materials is hard to control with external magnetic fields. Using x-ray magnetic linear dichroism microscopy, we show that staggered effective fields generated by electrical current can induce modification of the antiferromagnetic domain structure in microdevices fabricated from a tetragonal CuMnAs thin film. A clear correlation between the average domain orientation and the anisotropy of the electrical resistance is demonstrated, with both showing reproducible switching in response to orthogonally applied current pulses. However, the behavior is inhomogeneous at the submicron level, highlighting the complex nature of the switching process in multidomain antiferromagnetic films.

Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells.

BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we demonstrate that melanoma cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naïve cells. We also observed these findings in clinical melanoma specimens. Moreover, the increased expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and was instead correlated with the noncanonical Hh pathway, involving TGFß/SMAD (transforming growth factor-ß/Sma- and Mad-related family) signaling. Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells, an effect associated with both growth arrest and senescence. Treatment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor Gant61 led to decreased invasion of the melanoma cells in a three-dimensional skin reconstruct model and was associated with a decrease in metalloproteinase (MMP2/MMP9) expression and microphthalmia transcription factor upregulation. Gant61 monotherapy did not alter the drug sensitivity of naïve cells, but could reverse the resistance of melanoma cells chronically treated with vemurafenib. We further noted that alternating dosing schedules of Gant61 and vemurafenib prevented the onset of BRAFi resistance, suggesting that this could be a potential therapeutic strategy for the prevention of therapeutic escape. Our results suggest that targeting the Hh pathway in BRAFi-resistant melanoma may represent a viable therapeutic strategy to restore vemurafenib sensitivity, reducing or even inhibiting the acquired chemoresistance in melanoma patients.

Electrical switching of an antiferromagnet.

Antiferromagnets are hard to control by external magnetic fields because of the alternating directions of magnetic moments on individual atoms and the resulting zero net magnetization. However, relativistic quantum mechanics allows for generating current-induced internal fields whose sign alternates with the periodicity of the antiferromagnetic lattice. Using these fields, which couple strongly to the antiferromagnetic order, we demonstrate room-temperature electrical switching between stable configurations in antiferromagnetic CuMnAs thin-film devices by applied current with magnitudes of order 10(6) ampere per square centimeter. Electrical writing is combined in our solid-state memory with electrical readout and the stored magnetic state is insensitive to and produces no external magnetic field perturbations, which illustrates the unique merits of antiferromagnets for spintronics.

Developing and assessing the utility of a You-Tube based clinical genetics video channel for families affected by inherited tumours.

We have designed and implemented the first worldwide You Tube channel with 22 videos covering common questions asked in familial cancer susceptibility clinics. We discuss the use of the videos including demographics of registered You Tube users, and what lessons have been learnt about how the general public uses medical information online. The most popular video on inheritance patterns has been watched on average 84 times per month. The mostly highly viewed videos include inheritance patterns, breast cancer screening and hereditary non-polyposis colorectal cancer. Registered viewers were more commonly male and the average age of the registered user was 45-54 years; similar to that seen in Genetics Clinics suggesting that age may not be a major barrier to access to this type of information for patients. The videos have been viewed in more than 140 countries confirming that there is clearly an audience for this type of information. Patient feedback questionnaires indicate that these videos provide a useful aide memoir for the clinic appointment, and most people would recommend them to others. In summary, You Tube videos are easy and cost effective to make. They have the ability to disseminate genetics education to a worldwide audience and may be a useful adjunct to clinical appointments.

First Report of Fusarium Wilt in the Broomrape Parasite Growing on Brassica spp. in India.

Broomrape (Orobanche aegyptiaca Pers.), an important obligate root parasitic weed in India, has a wide host range including several members of the Solanaceae, Leguminaceae, and Brassicaceae families, among others. Orobanche plants produce thousands of tiny seeds (250 × 300 µm), which can remain viable in the soil for as long as 13 years (3). Rapeseed-mustard (Brassica spp.) is one of the major oilseed crops in India, cultivated on 5.77 million ha with 6.59 million t produced during 2009-2010. Broomrape has been observed in India as a major angiospermic parasitic plant on rapeseed-mustard, tobacco, tomato, and potato. During a field visit to an experimental farm at the Directorate of Rapeseed-Mustard Research, Bharatpur (27°12'N, 77°27'E) in the winter of 2009-2010, symptoms of wilt disease were observed on Orobanche plants, 32.6% of which had wilted completely following root infection. Initial symptoms appeared as a browning of the flowering stalk with wilting. Direct observation of below ground plant parasite tissues revealed a necrosis starting at the radical and advancing to the collar region that shredded later on. Tissue fragments, excised from the internal portions of the diseased tissue, were surface sterilized with 0.1% HgCl2, plated on 2% potato dextrose agar (PDA) adjusted to pH 7.0, and incubated at 22 ± 2°C for 7 days. The colonies that grew on PDA plates produced a bright purple color. Single-spore culturing of the fungus yielded Fusarium solani on the basis of morphological characteristics (2). The Fungal Identification Service, Mycology and Plant Pathology Group, Agharkar Research Institute, Pune, India (Accession No. 2156) confirmed the identity. The pathogenicity of the fungus was tested by inoculating five healthy Orobanche plants that were parasitizing Brassica spp. at the radicle region with 10-ml spore suspensions (2 × 105 conidia/ml of sterile distilled water) derived from 7-day-old cultures of the fungus. Control plants were treated with sterile distilled water. F. solani-inoculated radicles developed typical wilting symptoms within 2 weeks of treatment, while the control as well as the Brassica spp. plants remained healthy. F. solani was reisolated from inoculated wilted plants, thus fulfilling Koch's postulates. To our knowledge, on the basis of the literature, this is the first report from India showing that F. solani infects O. aegyptica on Brassica spp. There are reports of fungi (50 different species) infecting different hosts in Southern Italy, including F. oxysporum and F. solani, which have been found to be pathogenic to O. ramose. The most pathogenic Fusarium isolates significantly increased the number of dead spikes of broomrape (1). Control of Orobanche spp. poses a challenge because of the lack of effective and economic control measures. F. solani thus offers a potentially promising management strategy that should be explored in the future for the control of O. aegyptiaca. References: (1) A. Boari et al. Biol. Control 30:212, 2004. (2) P. E. Nelson et al. Fusarium Species: An Illustrated Manual for Identification. 1st ed. Pennsylvania State University Press, University Park, 1983. (3) M.C. Press et al. Parasitic Plants. Chapman and Hall, London, UK, 1995.

Assessment of dietary compliance to gluten free diet and psychosocial problems in Indian children with celiac disease.

OBJECTIVE: To assess dietary compliance to Gluten Free Diet (GFD), to identify barriers to compliance and to study the impact of diet on the psychosocial behavior of children with celiac disease. METHODS: Children diagnosed with celiac disease and followed up for more than 6 months, were assessed for dietary compliance. After this assessment, patients were subjected to an interview, consisting of self administered questionnaire, by the investigator who was blinded to initial results of initial assessment. Psychosocial parameters were assessed by standard Pediatric Symptom Checklist (PSC) containing 35 items. Dietary compliant and non-compliant groups were compared for assessed factors affecting the dietary compliance. Cases were also compared to healthy controls for psychosocial parameters. RESULTS: A total of 70 patients were assessed for dietary compliance: 53(75%) were found to be dietary compliant, 13(18%) dietary non-compliant while 4 had doubtful dietary compliance. Final analysis was done for 64 patients who had complete assessment; 4 patients with doubtful dietary compliance and 2 patients who had incomplete assessment, were excluded. Dietary compliance was higher in younger children (>80%) compared to adolescents (44%); in children with higher maternal education; in parents having better knowledge and understanding of disease. Compliance was better in nuclear families; with less number of siblings (68.3% of compliant had <2 siblings compared to 23% in non-compliant); in families with higher per capita income. Dietary compliance was also better in children who presented with typical symptoms of celiac disease (72% of dietary compliant presented with loose motion as presenting symptom compared to only 15% in non-compliant). Celiac children had problems related to adjustment such as difficulty in maintaining diet at school, restaurants, trips, etc.45% patients complained that their teachers don't understand the nature of their disease. Pediatric Symptom Checklist (PSC) score was above cut-off in 4 children of dietary non-compliant group. Few individual PSC items such as complaints of aches and pains; is irritable, angry; does not listen to the rules, blames other for mistakes; teases others; refuses to share, were more common in celiac children than control. CONCLUSIONS: Noncompliance to gluten free dietary regimen is seen in 18 % of cases. Dietary noncompliance is more common in the adolescent age group, in joint families and those who have more number of siblings. Dietary restrictions have impact on child's social activities and thus psychosocial parameters (PSC score) are better in the dietary compliant group.

Short communication: low-fat ice cream flavor not modified by high hydrostatic pressure treatment of whey protein concentrate.

The purpose of this study was to examine flavor binding of high hydrostatic pressure (HHP)-treated whey protein concentrate (WPC) in a real food system. Fresh Washington State University (WSU, Pullman) WPC, produced by ultrafiltration of separated Cheddar cheese whey, was treated at 300 MPa for 15 min. Commercial WPC 35 powder was reconstituted to equivalent total solids as WSU WPC (8.23%). Six batches of low-fat ice cream were produced: A) HHP-treated WSU WPC without diacetyl; B) and E) WSU WPC with 2 mg/L of diacetyl added before HHP; C) WSU WPC with 2 mg/L of diacetyl added after HHP; D) untreated WSU WPC with 2 mg/L of diacetyl; and F) untreated commercial WPC 35 with 2 mg/L of diacetyl. The solution of WSU WPC or commercial WPC 35 contributed 10% to the mix formulation. Ice creams were produced by using standard ice cream ingredients and processes. Low-fat ice creams containing HHP-treated WSU WPC and untreated WSU WPC were analyzed using headspace-solid phase microextraction-gas chromatography. Sensory evaluation by balanced reference duo-trio test was carried out using 50 untrained panelists in 2 sessions on 2 different days. The headspace-solid phase microextraction-gas chromatography analysis revealed that ice cream containing HHP-treated WSU WPC had almost 3 times the concentration of diacetyl compared with ice cream containing untreated WSU WPC at d 1 of storage. However, diacetyl was not detected in ice creams after 14 d of storage. Eighty percent of panelists were able to distinguish between low-fat ice creams containing untreated WSU WPC with and without diacetyl, confirming panelists' ability to detect diacetyl. However, panelists were not able to distinguish between low-fat ice creams containing untreated and HHP-treated WSU WPC with diacetyl. These results show that WPC diacetyl-binding properties were not enhanced by 300-MPa HHP treatment for 15 min, indicating that HHP may not be suitable for such applications.

Novel cytogenetic finding: an unusual X;X-translocation in Mehsana buffalo (Bubalus bubalis).

Cytogenetic investigations of a phenotypically normal Mehsana river buffalo calf (Bubalusbubalis) revealed an XXY chromosome complement due to X;X-translocation in all screened metaphase plates. The chromosomal anomaly was identified by GTG-banding while CBG- and RBG-banding revealed two heterochromatin blocks and that one of the two X chromosomes was late replicating, respectively. The normal cytogenetic profiles of sire, dam and relatives of the calf suggest that the anomaly could have arisen spontaneously during oogenesis. This is the first report on a male river buffalo calf having an XXY chromosome complement with translocation between the two X chromosomes.

The nematode-trapping efficacy of two chlamydospore-forming fungi against Haemonchus contortus in sheep.

An in vitro study was carried out to determine efficacy of Indian isolates of the nematode-trapping fungi Arthrobotrys musiformis and Duddingtonia flagrans to capture infective larvae of Haemonchus contortus. These fungi have previously been screened and selected for their survival in the gastrointestinal tract of sheep without losing growth and nematode capturing potential. Following the feeding of chlamydospores of these two fungi alone or in combination in sheep experimentally infected with Haemonchus contortus, coprocultures were set up to enumerate the infective third stage larvae. The number of larvae captured from faeces of fungus-fed sheep was significantly higher compared with fungus-unfed controls irrespective of the fungus used. The fungal combination produced no antagonistic effect and thus can be used as efficiently as the fungi alone in the biological control of animal parasitic nematodes.

Implications of fungicidal effects of benzimidazole compounds on Duddingtonia flagrans in integrated nematode parasite management in livestock.

An in vitro trial with carbendazim fungicide on the growth profile of the predatory fungus Duddingtonia flagrans was undertaken and in vivo trials in sheep and buffaloes, fed on chlamydospores of D. flagrans and administered albendazole anthelmintic, were conducted. Although no growth inhibition was detected at a carbendazim concentration of 0.05 ppm, growth inhibition was recorded of 50% and above at concentrations of 0.25 and 1.00 ppm (p < 0.001) and of around 90% at concentrations of 2.00 to 5.00 ppm (p <0.0001). Scanty recovery of the fungus was made from faecal culture 48 h following a single dose of albendazole both in sheep and buffaloes. However, profuse fungal recovery was made from 96 h post dosing onwards. When the drug was used as an intraruminal slow-release capsule, no faecal fungal recovery could be made from day 3 after administration of the capsule, when the albendazole sulphoxide concentration was around 1.0 microg/ml. However, profuse and scanty fungal recovery could be made on days 1 and 2, respectively, after administration of the capsule, when the plasma albendazole sulphoxide concentration was around 0.4 and 0.9 microg/ml, respectively. The implications for use of a combination of anthelmintics and biological control in sustainable parasite control programmes are discussed.

Ethanol vapour-fixation of rat lung for immunocytochemistry investigations.

Ethanol-vapour fixation of rat lung has been successfully employed in the immunocytochemical detection of the gastrin mucin antigen termed mucin 5AC without the need of additional antigen retrieval steps. This procedure gives good morphological preservation and provides all the benefits associated with the microscopic examination of inflated lung tissue. This simple fixation technique provides another option for use in immunocytochemical investigations of rodent lung and could be adapted for other species.

Transcriptional regulation of the glucokinase gene by biotin in starved rats.

The purpose of this work was to investigate whether biotin, a water-soluble vitamin, regulates the glucokinase gene. Biotin was administered intraperitoneally to starved rats, and the time course of glucokinase induction was followed over a time period of 12 h. The glucokinase mRNA was increased 19.6-fold during the first 1 h after biotin administration, afterwards rapidly decayed, and was hardly detectable by 4 h. The amount of glucokinase activity as determined by conventional enzyme activity assay increased in a time-dependent fashion, reaching 4-fold by 2 h of biotin administration. The transcriptional activity of the gene as measured by a nuclear run-on assay was increased about 6.7-fold within 45 min of biotin administration. These findings indicate that biotin can regulate the glucokinase gene at the transcriptional stage in the starved rat.