A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense.

In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in contrast to the antibacterial peptides, the antifungal peptide drosomycin remains inducible in a homozygous imd mutant background. These results point to the existence of two different pathways leading to the expression of two types of target genes, encoding either the antibacterial peptides or the antifungal peptide drosomycin.

p53 expression is required for thymocyte apoptosis induced by adenosine deaminase deficiency.

Adenosine deaminase (ADA, EC 3.5.4.4) is a ubiquitous enzyme in the purine catabolic pathway. In contrast to the widespread tissue distribution of this enzyme, inherited ADA deficiency in human results in a tissue-specific severe combined immunodeficiency. To explain the molecular basis for this remarkable tissue specificity, we have used a genetic approach to study ADA deficiency. We demonstrate that ADA deficiency causes depletion of CD8low transitional and CD4+CD8+ double-positive thymocytes by an apoptotic mechanism. This effect is mediated by a p53-dependent pathway, since p53-deficient mice are resistant to the apoptosis induced by ADA deficiency. DNA damage, known to be caused by the abnormal accumulation of dATP in ADA deficiency, is therefore responsible for the ablation of T-cell development and for the immunodeficiency. The two thymocyte subsets most susceptible to apoptosis induced by ADA deficiency are also the two thymocyte subsets with the lowest levels of bcl-2 expression. We show that thymocytes from transgenic mice that overexpress bcl-2 in the thymus are rescued from apoptosis induced by ADA deficiency. Thus, the tissue specificity of the pathological effects of ADA deficiency is due to the low bcl-2 expression in CD8low transitional and CD4+CD8+ double-positive thymocytes.

p53 deficiency does not affect the accumulation of point mutations in a transgene target.

DNA repair is required by organisms to prevent the accumulation of mutations and to maintain the integrity of genetic information. Mammalian cells that have been treated with agents that damage DNA have an increase in p53 levels, a p53-dependent arrest at G1 in the cell cycle, and a p53-dependent apoptotic response. It has been hypothesized that this block in cell cycle progression is necessary to allow time for DNA repair or to direct the damaged cell to an apoptotic pathway. This hypothesis predicts that p53-deficient cells would have an abnormal apoptotic response and exhibit a "mutator" phenotype. Using a sensitive assay for the accumulation of point mutations, small deletions, and insertions, we have directly tested whether p53-deficient cells exhibit an increased frequency of mutation before and after exposure to DNA-damaging agents. We report that wild-type and p53-deficient fibroblasts, thymocytes, and tumor tissue have indistinguishable rates of point mutation accumulation in a transgenic lacI target gene. These results suggest that the role of p53 in G1 checkpoint control and tumor suppression does not affect the accumulation of point mutations.

Deficiency of retinoblastoma protein leads to inappropriate S-phase entry, activation of E2F-responsive genes, and apoptosis.

The retinoblastoma susceptibility gene (Rb) participates in controlling the G1/S-phase transition, presumably by binding and inactivating E2F transcription activator family members. Mouse embryonic fibroblasts (MEFs) with no, one, or two inactivated Rb genes were used to determine the specific contributions of Rb protein to cell cycle progression and gene expression. MEFs lacking both Rb alleles (Rb-/-) entered S phase in the presence of the dihydrofolate reductase inhibitor methotrexate. Two E2F target genes, dihydrofolate reductase and thymidylate synthase, displayed elevated mRNA and protein levels in Rb- MEFs. Since absence of functional Rb protein in MEFs is sufficient for S-phase entry under growth-limiting conditions, these data indicate that the E2F complexes containing Rb protein, and not the Rb-related proteins p107 and p130, may be rate limiting for the G1/S transition. Antineoplastic drugs caused accumulation of p53 in the nuclei of both Rb+/+ and Rb-/- MEFs. While p53 induction led to apoptosis in Rb-/- MEFs, Rb+/- and Rb+/+ MEFs underwent cell cycle arrest without apoptosis. These results reveal that diverse growth signals work through Rb to regulate entry into S phase, and they indicate that absence of Rb protein produces a constitutive DNA replication signal capable of activating a p53-associated apoptotic response.

Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone.

Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in rats after subcutaneous administration, the analogs JI-22, [Dat1, Orn12,21, Abu15, Nle27, Agm29]hGH-RH-(1-29); JI-34, [Dat1, Orn12,21,Abu15,Nle27, Asp28, Agm29]hGH-RH-(1-29); JI-36, [Dat1, Thr8, Orn12,21, Abu15,Nle27,Asp28,Agm29]hGH-RH-(1-29); and JI-38, [Dat1,Gln8, Orn12,21,Abu15,Nle27,Asp28,Agm29]hGH-RH-(1 -29) displayed a potency 44.6,80.9,95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15 min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found to have higher binding affinities for GH-RH receptors on rat pituitary cells than hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be considered for therapy of patients with growth hormone deficiency.

Effect of commercial amino acids on iron nutrition of tomato plants grown under lime-induced iron deficiency

The objective of this work was to study the effect of root and foliar application of two commercial products containing amino acids from plant and animal origin on iron (Fe) nutrition of tomato seedlings cultivated in two nutrient media: lime and normal nutrient solutions. In the foliar-application experiment, each product was sprayed with 0.5 and 0.7 mL L–1 2, 7, 12, and 17 d after transplanting. In the root application experiment, 0.1 and 0.2 mL L–1 of amino acids products were added to the nutrient solutions. In both experiments, untreated control plants were included as well. Foliar and root application of the product containing amino acids from animal origin caused severe plant-growth depression and nonpositive effects on Fe nutrition were found. In contrast, the application of the product from plant origin stimulated plant growth. Furthermore, significantly enhanced root and leaf FeIII-chelate reductase activity, chlorophyll concentration, leaf Fe concentration, and FeII : Fe ratio were found in tomato seedlings treated with the product from plant origin, especially when the amino acids were directly applied to the roots. These effects were more evident in plants developed under lime-induced Fe deficiency. The positive results on Fe uptake may be related to the action of glutamic acid, the most abundant amino acid in the formulation of the product from plant origin.

Risālat Bulūgh al-amānī fī manāqib al-Shaykh Sīdī Aḥmad al-Tijānī

Aḥmad Adīb al-Makkī.

Durr al-nājī ʻalá matn Īsāghūjī

li-ʻUmar ibn Ṣāliḥ al-Fayḍī al-Tūqādī.

Sharḥ Īsāghūjī : manuscript, 1768

Missing one leaf or leaves at the beginning.

Kitāb Ghāyat al-maʼmūl fī sharḥ Zubdat al-uṣūl / al-matn li-Mawlānā al-Aqdas al-Shaykh Bahāʼ al-Dīn Khātimat al-mujtahidīn wa-al-sharḥ li-Sayyidinā al-Shaykh Muḥammad Jawād al-Kāẓimī : manuscript, 1651

Written in one column, 21 lines per pages, in black ink.

Kitāb Ghāyat al-maʼmūl fī sharḥ Waraqāt al-uṣūl / taʼlīf al-Shaykh al-Imām al-ʻĀlim al-ʻAllāmah al-Ḥibr al-Baḥr al-Fahhāmah Shaykh Mashāyikh al-Islām Abī al-ʻAbbās Aḥmad ibn Aḥmad al-Anṣārī al-Ramlī al-Shāfiʻī : manuscript, 1613

Written in one column, 21 lines per page, in black rubricated in red. First three leaves and last leaf framed within a double red line.

Kitāb Ghāyat al-maghnam fī al-ism al-aʻẓam / lil-Shaykh al-Imām al-ʻĀlim al-Rabbānī ʻAlī ibn Muḥammad ibn ʻAbd al-ʻAzīz ibn Fattūḥ ibn al-Durayhim : manuscript, undated

بسم الله الرحمن الرحيم اشرف نور الله وظهر كلام الله ولمب امر الله وبعد حلم الله ... :Incipit

Hādhā Ghāyat tahdhīb al-kalām fī taḥrīr al-manṭiq wa-al-kalām wa-taqrīb al-marām min taqrīr ʻaqāʼid al-Islām : manuscript, undated

Written in one column, from 14 to 19 lines per pages, in black and red.

Rasāʼil mufīdah fī bayān mawḍūʻ ʻilm al-tafsīr wa-taʻrīfihi wa-istimdādihi wa-ghāyatihi / lil-Imām al-ʻĀlim al-ʻAllāmah mufīd al-ṭālibīn Muḥammad ibn Khalīfah ibn Ṣadr al-mudarrisīn al-Shaykh Saʻd al-Dīn al-Marḥūmī al-Shawbarī : manuscript, undated

Written in one column, 21 lines per page, in black and red.

Sharḥ ʻalá Īsāghūjī : manuscript, 1778

According to colophon (f. 28r), copy completed on 24 Muḥarram 1192 [February 22, 1778] in the hand of Muḥammad Amīn ibn ʻAlī Ṭāhir ibn Ḥusayn ibn Muḥammad Qāsim.