Mammalian cells are frequently at risk of DNA damage from both endogenous and exogenous sources. Accordingly, cells have evolved the DNA damage response (DDR) pathways to monitor and assure the integrity of their genome. In cells, the intact and effective DDR is essential for the maintenance of genomic stability and it acts as a critical barrier to suppress the development of cancer in humans. Two central kinases for the DDR pathway are ATM and ATR, which can phosphorylate and activate many downstream proteins for cell cycle arrest, DNA repair, or apoptosis if the damages are irreparable. In the last several years, we and others have made significant progress to this field by identifying BRIT1 (also known as MCPH1) as a novel key regulator in the DDR pathway. BRIT1 protein contains 3 breast cancer carboxyl terminal (BRCT) domains which are conserved in BRCA1, MDC1, 53BP1, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. Our in vitro studies revealed BRIT1 to be a chromatin-binding protein required for recruitment of many important DDR proteins (ATM, MDC1, NBS1, RAD51, BRCA2) to the DNA damage sites. We recently also generated the BRIT1 knockout mice and demonstrated its essential roles in homologous recombination DNA repair and in maintaining genomic stability in vivo. In humans, BRIT1 is located on chromosome 8p23.1, where loss of hetero-zigosity is very common in many types of cancer. In this review, we will summarize the novel roles of BRIT1 in DDR, describe the relationship of BRIT1 deficiency with cancer development, and also discuss the use of synthetic lethality approach to target cancers with HR defects due to BRIT1 deficiency.
Animals ; Chromosomal Proteins, Non-Histone/genetics/metabolism/*physiology ; DNA Damage/genetics/*physiology ; DNA Repair/genetics/*physiology ; Humans ; Mice ; Models, Biological ; Neoplasms/*genetics ; Nerve Tissue Proteins/genetics/metabolism/*physiology

Mammalian cells are frequently at risk of DNA damage from both endogenous and exogenous sources. Accordingly, cells have evolved the DNA damage response (DDR) pathways to monitor and assure the integrity of their genome. In cells, the intact and effective DDR is essential for the maintenance of genomic stability and it acts as a critical barrier to suppress the development of cancer in humans. Two central kinases for the DDR pathway are ATM and ATR, which can phosphorylate and activate many downstream proteins for cell cycle arrest, DNA repair, or apoptosis if the damages are irreparable. In the last several years, we and others have made significant progress to this field by identifying BRIT1 (also known as MCPH1) as a novel key regulator in the DDR pathway. BRIT1 protein contains 3 breast cancer carboxyl terminal (BRCT) domains which are conserved in BRCA1, MDC1, 53BP1, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. Our in vitro studies revealed BRIT1 to be a chromatin-binding protein required for recruitment of many important DDR proteins (ATM, MDC1, NBS1, RAD51, BRCA2) to the DNA damage sites. We recently also generated the BRIT1 knockout mice and demonstrated its essential roles in homologous recombination DNA repair and in maintaining genomic stability in vivo. In humans, BRIT1 is located on chromosome 8p23.1, where loss of hetero-zigosity is very common in many types of cancer. In this review, we will summarize the novel roles of BRIT1 in DDR, describe the relationship of BRIT1 deficiency with cancer development, and also discuss the use of synthetic lethality approach to target cancers with HR defects due to BRIT1 deficiency.
Animals ; Chromosomal Proteins, Non-Histone/genetics/metabolism/*physiology ; DNA Damage/genetics/*physiology ; DNA Repair/genetics/*physiology ; Humans ; Mice ; Models, Biological ; Neoplasms/*genetics ; Nerve Tissue Proteins/genetics/metabolism/*physiology

Anemia, Aplastic ; complications ; surgery ; Bone Marrow Transplantation ; Child ; Hepatitis E ; complications ; surgery ; Humans ; Liver Failure, Acute ; complications ; surgery ; Liver Transplantation ; Male ; Tissue Donors ; Treatment Outcome

Fallen leaves of Ficus altissima, F. virens, F. benjamina, F. fistulosa and F. semicordata, were collected in Chiang Mai Province in northern Thailand and examined for fungi. Eighty taxa were identified, comprising 56 anamorphic taxa, 23 ascomycetes and 1 basidiomycete. Common fungal species occurring on five host species with high frequency of occurrence were Beltraniella nilgirica, Lasiodiplodia theobromae, Ophioceras leptosporum, Periconia byssoides and Septonema harknessi. Colletotrichum and Stachybotrys were also common genera. The leaves of different Ficus species supported diverse fungal taxa, and the fungal assemblages on the different hosts showed varying overlap. The fungal diversity of saprobes at the host species level is discussed.
Ascomycota ; isolation & purification ; Basidiomycota ; isolation & purification ; Ecosystem ; Ficus ; microbiology ; Fungi ; classification ; isolation & purification ; Mitosporic Fungi ; isolation & purification ; Plant Leaves ; microbiology ; Species Specificity ; Thailand

We present an overview of previous research results on the molecular phylogenetic analyses in Agaricales and its higher ranks (Agaricomycetes/Agaricomycotina/Basidiomycota) along with the most recent treatments of taxonomic systems in these taxa. Establishing phylogenetic hypotheses using DNA sequences, from which an understanding of the natural evolutionary relationships amongst clades may be derived, requires a robust dataset. It has been recognized that single-gene phylogenies may not truly represent organismal phylogenies, but the concordant phylogenetic genealogies from multiple-gene datasets can resolve this problem. The genes commonly used in mushroom phylogenetic research are summarized.
Agaricales ; classification ; genetics ; Basidiomycota ; classification ; genetics ; DNA, Fungal ; genetics ; Evolution, Molecular ; Models, Genetic ; Phylogeny ; Species Specificity

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.
Astringents ; China ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/pharmacology* ; Taste

Selecting the right applicants is an important part of medical student admission. While one universally accepted selection criterion is academic capacity, there are other criteria such as communication skills and local criteria (e.g., socio-cultural values) that are no less important. This article reviews the policies and methods of selection to medical schools in seven countries with varying socio-economic conditions and healthcare systems. Senior academics involved in medical education in Indonesia, Japan, Malaysia, the Philippines, Singapore, Sri Lanka, and Taiwan completed a pre-agreed pro-forma per each country to describe the country’s admission policies and methods. The details were then compared and contrasted. This review identifies tension between many of the policies and methods used in medical school admissions, such as between the need to assess non-cognitive abilities and widen access, and between the need for more medical professionals and the requirement to set high entry standards. Finding the right balance requires careful consideration of all variables, including the country’s human resource needs; socio-economic status; graduates’ expected competencies; and the school’s vision, mission, and availability of resources.

BACKGROUND/OBJECTIVES: Fruit and vegetable consumption of children in the United States falls below recommendations. The U.S. Department of Agriculture Fresh Fruit and Vegetable Program (FFVP) is a national free-fruit and vegetable school distribution program designed to address this problem. This permanent, legislated program provides funding to qualified elementary schools for provision of additional fruit and vegetables outside of school meals. The objective of this study was to understand children's perceptions of FFVP after the intervention and formulate recommendations that may improve success of the intervention. SUBJECTS/METHODS: Secondary data were obtained from 5,265 4th-6th graders at 51 randomly-selected FFVP intervention schools in Indiana. Anonymous questionnaires were completed late in the 2011-2012 academic year. Multilevel logistic regressions were used to determine associations between students' perceptions of program effects (4 close-ended items) and their preference toward the program. Content analysis was applied to a single open-ended item for program comments. RESULTS: Over 47% of students reported greater intake of fruit and vegetables due to FFVP, and over 66% reported liking the program. Student-reported program effects were positively associated with preference for the program (P < 0.01). Themes that emerged during analysis of 3,811 comments, included, students liked: the opportunity to try different kinds of fruit and vegetables, types and flavors of fruits served, and benefits of eating fruit. Fewer students liked the types of vegetables and their benefits. A small group disliked the program citing poor flavor of vegetables and quality of fruits. Important suggestions for the program include serving more dipping sauces for vegetables, cooking vegetables, and providing a greater variety of produce. CONCLUSIONS: The degree that students liked FFVP may predict the program's effects on fruit and vegetable intake. FFVP may become more acceptable to students by incorporating their suggestions. Program planners should consider these options for achieving program goals.
Accidental Falls ; Agriculture ; Anonyms and Pseudonyms ; Child ; Cooking ; Eating ; Financial Management ; Fruit* ; Humans ; Indiana ; Logistic Models ; Meals ; Program Evaluation ; United States Department of Agriculture* ; United States* ; Vegetables*

BACKGROUND/OBJECTIVES: Fruit and vegetable consumption of children in the United States falls below recommendations. The U.S. Department of Agriculture Fresh Fruit and Vegetable Program (FFVP) is a national free-fruit and vegetable school distribution program designed to address this problem. This permanent, legislated program provides funding to qualified elementary schools for provision of additional fruit and vegetables outside of school meals. The objective of this study was to understand children's perceptions of FFVP after the intervention and formulate recommendations that may improve success of the intervention. SUBJECTS/METHODS: Secondary data were obtained from 5,265 4th-6th graders at 51 randomly-selected FFVP intervention schools in Indiana. Anonymous questionnaires were completed late in the 2011-2012 academic year. Multilevel logistic regressions were used to determine associations between students' perceptions of program effects (4 close-ended items) and their preference toward the program. Content analysis was applied to a single open-ended item for program comments. RESULTS: Over 47% of students reported greater intake of fruit and vegetables due to FFVP, and over 66% reported liking the program. Student-reported program effects were positively associated with preference for the program (P < 0.01). Themes that emerged during analysis of 3,811 comments, included, students liked: the opportunity to try different kinds of fruit and vegetables, types and flavors of fruits served, and benefits of eating fruit. Fewer students liked the types of vegetables and their benefits. A small group disliked the program citing poor flavor of vegetables and quality of fruits. Important suggestions for the program include serving more dipping sauces for vegetables, cooking vegetables, and providing a greater variety of produce. CONCLUSIONS: The degree that students liked FFVP may predict the program's effects on fruit and vegetable intake. FFVP may become more acceptable to students by incorporating their suggestions. Program planners should consider these options for achieving program goals.
Accidental Falls ; Agriculture ; Anonyms and Pseudonyms ; Child ; Cooking ; Eating ; Financial Management ; Fruit* ; Humans ; Indiana ; Logistic Models ; Meals ; Program Evaluation ; United States Department of Agriculture* ; United States* ; Vegetables*

To prepare doxorubicin-loaded N-octyl-N'-succinyl chitosan polymeric micelle (DOX-OSC) and study the biodistribution of DOX-OSC in mice, DOX-OSC was prepared by dialysis method. By using doxorubicin injection (DOX-INJ) as control, DOX-OSC and DOX-INJ were administered to mice through caudal vein at a dose of 5 mg x kg(-1) body weight. The RP-HPLC method was established to determine the DOX levels in the plasma and other tissues of mice. The tissues distribution and targeting efficiency were evaluated by pharmacokinetic parameters (AUC, MRT) and targeting parameters (Re, Ce and Te). The drug loading and entrapment efficiency of DOX-OSC were (35.8 +/- 0.4)% and (75.3 +/- 1.1)%, respectively. The diameter and zeta potential of DOX-OSC were (174 +/- 12) nm and (-37.1 +/- 3.0) mV, respectively. The transmission electron microscope result showed DOX-OSC with spherical shape. The biodistribution results showed that the concentration of DOX of both DOX-OSC and DOX-INJ decreased rapidly in blood after iv administration. While free DOX levels in blood at 12-96 h were not detectable for DOX-INJ, in contrast, DOX level in blood at 96 h was still found for DOX-OSC. In contrast to DOX-INJ group, DOX-OSC showed a higher targeting efficiency in the liver and spleen. The AUCs of DOX in the liver and spleen were 20.0 and 47.4 times and the MRT were 11.2 and 37.2 times, respectively. And the levels of DOX-OSC in the heart and kidney tissues were significantly reduced. And the drug distribution of DOX-OSC in the heart and kidney tissues were 17.0% and 11.4%, respectively. Hence, DOX-OSC shows an excellent drug loading capabilities and a higher targeting efficiency in the liver and spleen. That the levels of DOX-OSC in the heart and kidney tissues are significantly reduced, might improve the treatment efficacy of DOX and decrease the side effects.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Chitosan ; analogs & derivatives ; chemistry ; Doxorubicin ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Female ; Liver ; metabolism ; Male ; Mice ; Micelles ; Particle Size ; Polymers ; Spleen ; metabolism ; Tissue Distribution