Displaying publications 1 - 20 of 1575 in total

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  1. Anwar A, Mungroo MR, Anwar A, Sullivan WJ, Khan NA, Siddiqui R
    ACS Infect Dis, 2019 Dec 13;5(12):2039-2046.
    PMID: 31612700 DOI: 10.1021/acsinfecdis.9b00263
    Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiamoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet-visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size distribution with the average diameter of around 100 nm. Guanabenz and its noble metal nanoconjugates exhibited potent antiamoebic effects in the range of 2.5 to 100 μM against both amoebae. Nanoparticle conjugation enhanced the antiamoebic effects of guanabenz, as more potent activity was observed at a lower effective concentration (2.5 and 5 μM) compared to the drug alone. Moreover, encystation and excystation assays revealed that guanabenz inhibits the interconversion between the trophozoite and cyst forms of A. castellanii. Cysticdal effects against N. fowleri were also observed. Notably, pretreatment of A. castellanii with guanabenz and its nanoconjugates exhibited a significant reduction in the host cell cytopathogenicity from 65% to 38% and 2% in case of gold and silver nanoconjugates, respectively. Moreover, the cytotoxic evaluation of guanabenz and its nanoconjugates revealed negligible cytotoxicity against human cells. Guanabenz is already approved for hypertension and crosses the blood-brain barrier; the results of our current study suggest that guanabenz and its conjugated gold and silver nanoparticles can be repurposed as a potential drug for treating brain-eating amoebic infections.
    Matched MeSH terms: Naegleria fowleri/growth & development; Acanthamoeba castellanii/growth & development
  2. Avicor SW, Wajidi MF, Jaal Z, Yahaya ZS
    Acta Biochim. Pol., 2016;63(2):243-6.
    PMID: 27059016 DOI: 10.18388/abp.2014_909
    Septins belong to GTPases that are involved in vital cellular activities, including cytokinesis. Although present in many organisms, they are yet to be isolated from Aedes albopictus. This study reports for the first time on a serendipitous isolation of a partial septin sequence from Ae. albopictus and its developmental expression profile. The Ae. albopictus partial septin sequence contains 591 nucleotides encoding 197 amino acids. It shares homology with several insect septin genes and has a close phylogenetic relationship with Aedes aegypti and Culex quinquefasciatus septins. The Ae. albopictus septin fragment was differentially expressed in the mosquito's developmental stages, with an increased expression in the adults.
    Matched MeSH terms: Aedes/growth & development
  3. Venil CK, Zakaria ZA, Ahmad WA
    Acta Biochim. Pol., 2015;62(2):185-90.
    PMID: 25979288 DOI: 10.18388/abp.2014_870
    Flexirubins are the unique type of bacterial pigments produced by the bacteria from the genus Chryseobacterium, which are used in the treatment of chronic skin disease, eczema etc. and may serve as a chemotaxonomic marker. Chryseobacterium artocarpi CECT 8497, an yellowish-orange pigment producing strain was investigated for maximum production of pigment by optimizing medium composition employing response surface methodology (RSM). Culture conditions affecting pigment production were optimized statistically in shake flask experiments. Lactose, l-tryptophan and KH2PO4 were the most significant variables affecting pigment production. Box Behnken design (BBD) and RSM analysis were adopted to investigate the interactions between variables and determine the optimal values for maximum pigment production. Evaluation of the experimental results signified that the optimum conditions for maximum production of pigment (521.64 mg/L) in 50 L bioreactor were lactose 11.25 g/L, l-tryptophan 6 g/L and KH2PO4 650 ppm. Production under optimized conditions increased to 7.23 fold comparing to its production prior to optimization. Results of this study showed that statistical optimization of medium composition and their interaction effects enable short listing of the significant factors influencing maximum pigment production from Chryseobacterium artocarpi CECT 8497. In addition, this is the first report optimizing the process parameters for flexirubin type pigment production from Chryseobacterium artocarpi CECT 8497.
    Matched MeSH terms: Chryseobacterium/growth & development
  4. Sivakumar P, Law YS, Ho CL, Harikrishna JA
    Acta. Biol. Hung., 2010 Sep;61(3):313-21.
    PMID: 20724277 DOI: 10.1556/ABiol.61.2010.3.7
    An efficient in vitro plant regeneration system was established for elite, recalcitrant Malaysian indica rice, Oryza sativa L. CV. MR 219 using mature seeds as explant on Murashige and Skoog and Chu N6 media containing 2,4-dichlorophenoxy acetic acid and kinetin either alone or in different combinations. L-proline, casein hydrolysate and L-glutamine were added to callus induction media for enhancement of embryogenic callus induction. The highest frequency of friable callus induction (84%) was observed in N6 medium containing 2.5 mg l(-1) 2,4-dichlorophenoxy acetic acid, 0.2 mg l(-1) kinetin, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate, 20 mg l(-1) L-glutamine and 30 g l(-1) sucrose under culture in continuous lighting conditions. The maximum regeneration frequency (71%) was observed, when 30-day-old N6 friable calli were cultured on MS medium supplemented with 3 mg l(-1) 6-benzyl aminopurine, 1 mg l(-1) naphthalene acetic acid, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate and 3% maltose. Developed shoots were rooted in half strength MS medium supplemented with 2% sucrose and were successfully transplanted to soil with 95% survival. This protocol may be used for other recalcitrant indica rice genotypes and to transfer desirable genes in to Malaysian indica rice cultivar MR219 for crop improvement.
    Matched MeSH terms: Oryza/growth & development; Seeds/growth & development
  5. Wei LS, Wee W, Siong JY, Syamsumir DF
    Acta Med Iran, 2011;49(10):670-4.
    PMID: 22071643
    Peperomia pellucida leaf extract was characterized for its anticancer, antimicrobial, antioxidant activities, and chemical compositions. Anticancer activity of P. pellucida leaf extract was determined through Colorimetric MTT (tetrazolium) assay against human breast adenocarcinoma (MCF-7) cell line and the antimicrobial property of the plant extract was revealed by using two-fold broth micro-dilution method against 10 bacterial isolates. Antioxidant activity of the plant extract was then characterized using α, α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging method and the chemical compositions were screened and identified using gas chromatography-mass spectrometry (GC-MS). The results of present study indicated that P. pellucida leaf extract possessed anticancer activities with half maximal inhibitory concentration (IC(50)) of 10.4 ± 0.06 µg/ml. The minimum inhibitory concentration (MIC) values were ranged from 31.25 to 125 mg/l in which the plant extract was found to inhibit the growth of Edwardsiella tarda, Escherichia coli, Flavobacterium sp., Pseudomonas aeruginosa and Vibrio cholerae at 31.25 mg/l; Klebsiella sp., Aeromonas hydrophila and Vibrio alginolyticus at 62.5 mg/l; and it was able to control the growth of Salmonella sp. and Vibrio parahaemolyticus at 125 mg/l. At the concentration of 0.625 ppt, the plant extract was found to inhibit 30% of DPPH, free radical. Phytol (37.88%) was the major compound in the plant extract followed by 2-Naphthalenol, decahydro- (26.20%), Hexadecanoic acid, methyl ester (18.31%) and 9,12-Octadecadienoic acid (Z,Z)-, methyl ester (17.61%). Findings from this study indicated that methanol extract of P. pellucida leaf possessed vast potential as medicinal drug especially in breast cancer treatment.
    Matched MeSH terms: Bacteria/growth & development
  6. Asad M, Oo CW, Kumar RS, Osman H, Ali MA
    Acta Pol Pharm, 2013 Mar-Apr;70(2):221-8.
    PMID: 23614277
    A series of some new bisadducts possessing five, six membered and coumarin subunits were synthesized by the condensation of heterocyclic aldehydes with active methylene compounds and characterized by IR, NMR and X-ray crystallographic studies and were assayed as antitubercular agents. Among the bisadducts, 4-hydroxy-3-[(4-hydroxy-2-oxo-2H-3-chromenyl)(3-thienyl)methyl]-2H-2-chromenone 3a was found to be the most promising compound, active against Mycobacterium tuberculosis (Mtb) H37Rv and isoniazid resistant Mycobacterium tuberculosis (INHR-Mtb) with minimum inhibitory concentration 5.22 and 8.34 microM, respectively.
    Matched MeSH terms: Mycobacterium tuberculosis/growth & development
  7. Ali MA, Ismail R, Choon TS, Yoon YK, Wei AC, Pandian S, et al.
    Acta Pol Pharm, 2011 May-Jun;68(3):343-8.
    PMID: 21648188
    A series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized by the reaction of 5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-indanone with hydroxylamine hydrochloride. The title compounds were tested for their in vitro anti-HIV activity. Among the compounds, (4g) showed a promising anti-HIV activity in the in vitro testing against IIIB and ROD strains. The IC50 of both IIIB and ROD were found to be 9.05 microM and > 125 microM, respectively.
    Matched MeSH terms: HIV-1/growth & development; HIV-2/growth & development
  8. Dieng H, Hassan RB, Hassan AA, Ghani IA, Abang FB, Satho T, et al.
    Acta Trop, 2015 May;145:68-78.
    PMID: 25617636 DOI: 10.1016/j.actatropica.2015.01.004
    Even with continuous vector control, dengue is still a growing threat to public health in Southeast Asia. Main causes comprise difficulties in identifying productive breeding sites and inappropriate targeted chemical interventions. In this region, rural families keep live birds in backyards and dengue mosquitoes have been reported in containers in the cages. To focus on this particular breeding site, we examined the capacity of bird fecal matter (BFM) from the spotted dove, to support Aedes albopictus larval growth. The impact of BFM larval uptake on some adult fitness traits influencing vectorial capacity was also investigated. In serial bioassays involving a high and low larval density (HD and LD), BFM and larval standard food (LSF) affected differently larval development. At HD, development was longer in the BFM environment. There were no appreciable mortality differences between the two treatments, which resulted in similar pupation and adult emergence successes. BFM treatment produced a better gender balance. There were comparable levels of blood uptake and egg production in BFM and LSF females at LD; that was not the case for the HD one, which resulted in bigger adults. BFM and LSF females displayed equivalent lifespans; in males, this parameter was shorter in those derived from the BFM/LD treatment. Taken together these results suggest that bird defecations successfully support the development of Ae. albopictus. Due to their cryptic aspects, containers used to supply water to encaged birds may not have been targeted by chemical interventions.
    Matched MeSH terms: Larva/growth & development
  9. Antinori S, Galimberti L, Milazzo L, Corbellino M
    Acta Trop, 2013 Feb;125(2):191-201.
    PMID: 23088834 DOI: 10.1016/j.actatropica.2012.10.008
    Plasmodium knowlesi was initially identified in the 30s as a natural Plasmodium of Macaca fascicularis monkey also capable of experimentally infecting humans. It gained a relative notoriety in the mid-30s as an alternative to Plasmodium vivax in the treatment of the general paralysis of the insane (neurosyphilis). In 1965 the first natural human infection was described in a US military surveyor coming back from the Pahang jungle of the Malaysian peninsula. P. knowlesi was again brought to the attention of the medical community when in 2004, Balbir Singh and his co-workers reported that about 58% of malaria cases observed in the Kapit district of the Malaysian Borneo were actually caused by P. knowlesi. In the following years several reports showed that P. knowlesi is much more widespread than initially thought with cases reported across Southeast Asia. This infection should also be considered in the differential diagnosis of any febrile travellers coming back from a recent travel to forested areas of Southeast Asia. P. knowlesi can cause severe malaria with a rate of 6-9% and with a case fatality rate of 3%. Respiratory distress, acute renal failure, shock and hyperbilirubinemia are the most frequently observed complications of severe P. knowlesi malaria. Chloroquine is considered the treatment of choice of uncomplicated malaria caused by P. knowlesi.
    Matched MeSH terms: Trophozoites/growth & development
  10. Choo KE, Davis TM, Ismail A, Tuan Ibrahim TA, Ghazali WN
    Acta Trop, 1999 Mar 15;72(2):175-83.
    PMID: 10206117
    The Typhidot test, which detects IgM and IgG antibodies to a Salmonella typhi-specific outer membrane protein, is as sensitive as, and more specific than, the Widal test in the diagnosis of enteric fever in Malaysian children. It is easier and quicker to perform. In order to increase diagnostic accuracy in an area of high endemicity, the Typhidot-M test has been developed in which IgG is first removed. This theoretically allows improved detection of IgM, and thus would differentiate new from recent infections. We evaluated both tests in 134 unselected febrile children admitted to the General Hospital Kota Bharu, Malaysia. The children were divided into two groups: (i) those who were blood and/or stool culture positive for S. typhi and/or who had clinical features strongly suggestive of enteric fever (n = 62); and (ii) those who were both culture-negative and had clinical evidence of another diagnosis (n = 72). The sensitivity and specificity of the Typhidot and Typhidot-M tests were identical at 90.3 and 93.1%, respectively. Both tests had comparable sensitivity but greater specificity than those of the Widal test (91.9 and 80.6%, respectively). When used together, a positive result for Typhidot and/or Typhidot-M was more specific than either test alone (95.2%) but specificity was lower (87.5%). We conclude that the Typhidot and Typhidot-M tests have comparatively high diagnostic accuracy, suggesting that IgM can be detected in children who may have a predominant IgG response to S. typhi. Using these tests in combination increases the negative predictive value but at the cost of a lower positive predictive value.
    Matched MeSH terms: Salmonella typhi/growth & development
  11. Mak JW, Choong MF, Lam PL, Suresh K
    Acta Trop, 1990 May;47(4):223-6.
    PMID: 1973024
    The leaf-monkeys, Presbytis cristata and Presbytis melalophos, experimentally infected with subperiodic Brugia malayi, have been used for studies on the pathoimmunology of the infection and the screening of potential filaricides during the last 6-8 years, and considerable information on the pattern of microfilaraemia and adult worm recoveries have been obtained. The prepatent periods in 97 P. cristata and 45 P. melalophos, each infected with about 200 infective larvae, were similar, these being approximately 70 and 68 days respectively. Although all infected animals became microfilaraemic, the peak geometric mean count was much higher in P. cristata than in P. melalophos, this being 182.0 and 65.8 per ml blood respectively. Mean adult worm recovery expressed as the percentage of the infective dose was 4.7% and 2.5%, respectively. Most worms were recovered from the sacral nodes/thoracic duct or inguinal lymph nodes in these animals. In view of the higher worm recovery and the higher peak microfilaraemia attained, it is concluded that P. cristata is a better model for the infection than P. melalophos.
    Matched MeSH terms: Brugia/growth & development*
  12. Lee HY, Loong SK, Ya'cob Z, Low VL, Teoh BT, Ahmad-Nasrah SN, et al.
    Acta Trop, 2021 Jul;219:105923.
    PMID: 33878305 DOI: 10.1016/j.actatropica.2021.105923
    Although the microbiome of blood-feeding insects serves an integral role in host physiology, both beneficial and pathogenic, little is known of the microbial community of black flies. An investigation, therefore, was undertaken to identify culturable bacteria from one of Malaysia's most common black flies, Simulium tani Takaoka and Davies, using 16S rDNA sequencing, and then evaluate the isolates for antibiotic resistance and virulence genes. A total of 20 isolates representing 11 bacterial species in four genera were found. Five isolates showed β-hemolysis on Columbia agar, and virulence genes were found in three of these isolates. Some degree of resistance to six of the 12 tested antibiotics was found among the isolates. The baseline data from this study suggest rich opportunities for comparative studies exploring the diversity and roles of the microbiome of S. tani and other Southeast Asian black flies.
    Matched MeSH terms: Bacteria/growth & development*
  13. Bänziger H
    Acta Trop, 1979 Mar;36(1):23-37.
    PMID: 35931
    1. Of the scarce Calyptra minuticornis, C. orthograpta and C. labilis, 51, 24, and 7 adults, respectively, were observed during some 600 night inspections at over 100 sites in 1965--1967 and 1971--1977. 2. Hitherto biologically completely unknown, and not recorded before in S.E. Asia, the latter two species flew in or near tropical monsoon forests in hilly regions (300--600 m) of N. Thailand (C. orthograpta also N. Laos). C. minuticornis was found in these and in tropical evergreen and semi-evergreen rain forests of S. Thailand and N.W. Malaysia. 3. In N. Thailand the three species were more common at the end of the cool season/start of the hot season and at the start of the rainy season. They were active mainly during the first half of the night 4. Flight and piercing behaviour, alighting, resting, enemies, and the lack of females, were similar to virtually identical with the "classical" skin-piercing blood-sucking C. eustrigata. 5. C. labilis was seen attacking elephant, C. orthograpta also water buffalo and sambar, C. minuticornis also zebu and tapir but not sambar. C. minuticornis settled on man also but did not pierce. 6. Through no piercing of hosts' skin has actually been seen in nature, indirect evidence suggests that the 3 moths are likely to be occasional blood-suckers. They pierced and sucked blood from the author's skin in experiments. 7. Reasons for lack of direct evidence may be: less developed hematophagy, less favoured hosts, lack of easy-to-pierce injured skin (which also trigger the piercing response), different climatic and phytoecological environment, fewer specimens than in the case of C. eustrigata. 8. Field observations and experiments indicate that the closely related, fruit-piercing Oraesia emarginata is not skin-piercing blood-sucking--a habit likely to be exhibited mainly in humid equatorial regions by a few Calyptra only.
    Matched MeSH terms: Moths/growth & development
  14. Loh HS, Mohd-Azmi ML, Sheikh-Omar AR, Zamri-Saad M, Tam YJ
    Acta Virol., 2007;51(1):27-33.
    PMID: 17432941
    The present study described the kinetics of Rat cytomegalovirus (RCMV) infection in newborn rats by monitoring infectious virus and viral antigens in various organs, viral DNA in the blood (DNAemia) and antibody response. These parameters were evaluated quantitatively using double-antibody sandwich ELISA (DAS-ELISA), real-time PCR, indirect ELISA and virus infectivity assay. For the first time DAS-ELISA was used for detection of RCMV antigen directly from organ samples. The relationships between the presence of viral antigens in the infected organs and antibody levels were established by the Spearman's rank test. It was found that the virus was present in the blood, spleen, liver, lungs, and kidneys earlier than in the salivary glands. Furthermore, the early immunity of the newborn rats led to a delayed seroconversion. We suggested that the prolonged presence of the virus in salivary glands could augment the antibody response that conversely might be responsible for a reduction of viremia. This study expanded our understanding of RCMV pathogenesis leading to improved therapeutic and preventive treatment regimens particularly for the neonatal Human cytomegalovirus (HCMV) infections. Additionally, the detection procedures developed in this study such as DAS-ELISA and real-time PCR could serve as alternative techniques for rapid screening of large number of samples.
    Matched MeSH terms: Muromegalovirus/growth & development*
  15. Hasmah MS, Omar AR, Wan KF, Hair-Bejo M, Aini I
    Acta Virol., 2004;48(2):85-9.
    PMID: 15462283
    It has been shown that a chicken anemia virus (CAV) isolates which had undergone 60 passages in MSB-1 cells (SMSC-1/P60, 3-1/P60) acquired 33-66 nucleotide substitutions at the coding region resulting in 13-16 amino acid changes as compared to the CAV isolates passaged only 5 times in MSB-1 cells (SMSC-1 and 3-1) (Chowdhury et al., Arch. Virol. 148, 2437-2448, 2003). In this study we found that a low CAV (BL-5) and a high CAV passage (BL-5/P90) differed by only 15 nucleotide substitutions resulting in 11 amino acid changes. Phylogenetic analysis based on VP1 also revealed that both isolates were close to each other but not to other CAV isolates from Malaysia, namely SMSC-1 and 3-1.
    Matched MeSH terms: Chicken anemia virus/growth & development*
  16. El Enshasy H, Malik K, Malek RA, Othman NZ, Elsayed EA, Wadaan M
    PMID: 26907552
    Human gastrointestinal microbiota (HGIM) incorporate a large number of microbes from different species. Anaerobic bacteria are the dominant organisms in this microbial consortium and play a crucial role in human health. In addition to their functional role as the main source of many essential metabolites for human health, they are considered as biotherapeutic agents in the regulation of different human metabolites. They are also important in the prevention and in the treatment of different physical and mental diseases. Bifidobacteria are the dominant anaerobic bacteria in HGIM and are widely used in the development of probiotic products for infants, children and adults. To develop bifidobacteria-based bioproducts, therefore, it is necessary to develop a large-scale biomass production platform based on a good understanding of the ideal medium and bioprocessing parameters for their growth and viability. In addition, high cell viability should be maintained during downstream processing and storage of probiotic cell powder or the final formulated product. In this work we review the latest information about the biology, therapeutic activities, cultivation and industrial production of bifidobacteria.
    Matched MeSH terms: Bacteria, Anaerobic/growth & development*; Bifidobacterium/growth & development*
  17. Ng WJ, Ken KW, Kumar RV, Gunasagaran H, Chandramogan V, Lee YY
    PMID: 25435614
    BACKGROUND: Different researches on therapeutic effects of honey have been conducted in different regions; however the study on the potential antibacterial activity of Malaysian honey is still limited. In this study, antibacterial activities of different monofloral honey samples were tested against several common human pathogenic bacteria.

    MATERIALS AND METHODS: The well-diffusion method, minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) techniques were employed to investigate the putative antibacterial activity of Malaysian monofloral honey from Koompassia excelsa (Becc.) Taub (Tualang), Melaleuca cajuputi Powell (Gelam) and Durio zibethinus Murr. (Durian). Honey samples were tested against Staphylococcus aureus ATCC6518 and ATCC25923, Staphylococcus epidermidis ATCC12228, Enterococcus faecium LMG16192, Enterococcus faecalis LMG16216 and ATCC29212, Escherichia coli ATCC25922, Salmonella enterica serovar Typhimurium ATCC14028 and Klebsiella pneumoniae ATCC13883.

    RESULTS: Marked variations were observed in the antibacterial activity of these honey samples. Durian honey failed to produce substantial antibacterial activity, whereas Tualang and Gelam honey showed a spectrum of antibacterial activity with their growth inhibitory effects against all of the tested bacterial species including vancomycin-resistant enterococci (VRE).

    CONCLUSION: Present findings suggested Gelam honey possesses highest antibacterial effect among the tested Malaysian honey samples.

    Matched MeSH terms: Bacteria/growth & development
  18. Taylor ML, Cooper RL, Schneider EL, Osborn JM
    Am J Bot, 2015 Oct;102(10):1685-702.
    PMID: 26419810 DOI: 10.3732/ajb.1500249
    A knowledge of pollen characters in early-diverging angiosperm lineages is essential for understanding pollen evolution and the role of pollen in angiosperm diversification. In this paper, we report and synthesize data on mature pollen and pollen ontogeny from all genera of Nymphaeales within a comparative, phylogenetic context and consider pollen evolution in this early-diverging angiosperm lineage. We describe mature pollen characters for Euryale, Barclaya, and Nymphaea ondinea, taxa for which little to no structural data exist.
    Matched MeSH terms: Pollen/growth & development*; Nymphaeaceae/growth & development*; Nymphaea/growth & development
  19. Reijnders MRF, Ansor NM, Kousi M, Yue WW, Tan PL, Clarkson K, et al.
    Am J Hum Genet, 2017 Sep 07;101(3):466-477.
    PMID: 28886345 DOI: 10.1016/j.ajhg.2017.08.007
    RAC1 is a widely studied Rho GTPase, a class of molecules that modulate numerous cellular functions essential for normal development. RAC1 is highly conserved across species and is under strict mutational constraint. We report seven individuals with distinct de novo missense RAC1 mutations and varying degrees of developmental delay, brain malformations, and additional phenotypes. Four individuals, each harboring one of c.53G>A (p.Cys18Tyr), c.116A>G (p.Asn39Ser), c.218C>T (p.Pro73Leu), and c.470G>A (p.Cys157Tyr) variants, were microcephalic, with head circumferences between -2.5 to -5 SD. In contrast, two individuals with c.151G>A (p.Val51Met) and c.151G>C (p.Val51Leu) alleles were macrocephalic with head circumferences of +4.16 and +4.5 SD. One individual harboring a c.190T>G (p.Tyr64Asp) allele had head circumference in the normal range. Collectively, we observed an extraordinary spread of ∼10 SD of head circumferences orchestrated by distinct mutations in the same gene. In silico modeling, mouse fibroblasts spreading assays, and in vivo overexpression assays using zebrafish as a surrogate model demonstrated that the p.Cys18Tyr and p.Asn39Ser RAC1 variants function as dominant-negative alleles and result in microcephaly, reduced neuronal proliferation, and cerebellar abnormalities in vivo. Conversely, the p.Tyr64Asp substitution is constitutively active. The remaining mutations are probably weakly dominant negative or their effects are context dependent. These findings highlight the importance of RAC1 in neuronal development. Along with TRIO and HACE1, a sub-category of rare developmental disorders is emerging with RAC1 as the central player. We show that ultra-rare disorders caused by private, non-recurrent missense mutations that result in varying phenotypes are challenging to dissect, but can be delineated through focused international collaboration.
    Matched MeSH terms: Zebrafish/growth & development
  20. Surendran S, Thomas E
    Am J Orthod Dentofacial Orthop, 2014 Jan;145(1):7-14.
    PMID: 24373650 DOI: 10.1016/j.ajodo.2013.09.007
    The objective of this study was to determine whether dental calcification can be used as a first-level diagnostic tool for assessment of skeletal maturity.
    Matched MeSH terms: Bicuspid/growth & development; Cuspid/growth & development; Dental Pulp/growth & development; Epiphyses/growth & development; Growth Plate/growth & development; Molar/growth & development; Tooth Root/growth & development; Tooth Apex/growth & development; Tooth Crown/growth & development; Finger Phalanges/growth & development
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