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<jats:p>The oriented peptide library technique was used to investigate the peptide-binding specificities of nine PDZ domains. Each PDZ domain selected peptides with hydrophobic residues at the carboxyl terminus. Individual PDZ domains selected unique optimal motifs defined primarily by the carboxyl terminal three to seven residues of the peptides. One family of PDZ domains, including those of the Discs Large protein, selected peptides with the consensus motif Glu-(Ser/Thr)-Xxx-(Val/Ile) (where Xxx represents any amino acid) at the carboxyl terminus. In contrast, another family of PDZ domains, including those of LIN-2, p55, and Tiam-1, selected peptides with hydrophobic or aromatic side chains at the carboxyl terminal three residues. On the basis of crystal structures of the PSD-95-3 PDZ domain, the specificities observed with the peptide library can be rationalized.</jats:p>

<jats:p> Human immune responses are heterogeneous and may involve antagonism between T helper (T <jats:sub>H</jats:sub> ) lymphocyte subsets and their cytokines. Atopy is characterized by immediate immunoglobulin E (IgE)-mediated hypersensitivity to agents such as dust mites and pollen, and it underlies the increasingly prevalent disorder asthma. Among Japanese schoolchildren, there was a strong inverse association between delayed hypersensitivity to <jats:italic>Mycobacterium tuberculosis</jats:italic> and atopy. Positive tuberculin responses predicted a lower incidence of asthma, lower serum IgE levels, and cytokine profiles biased toward T <jats:sub>H</jats:sub> 1 type. Exposure and response to <jats:italic>M. tuberculosis</jats:italic> may, by modification of immune profiles, inhibit atopic disorder. </jats:p>

<jats:p> Flowering plants exhibit one of two types of inflorescence architecture: indeterminate, in which the inflorescence grows indefinitely, or determinate, in which a terminal flower is produced. The indeterminate condition is thought to have evolved from the determinate many times, independently. In two mutants in distantly related species, <jats:italic>terminal flower 1</jats:italic> in <jats:italic>Arabidopsis</jats:italic> and <jats:italic>centroradialis</jats:italic> in <jats:italic>Antirrhinum</jats:italic> , inflorescences that are normally indeterminate are converted to a determinate architecture. The <jats:italic>Antirrhinum</jats:italic> gene <jats:italic>CENTRORADIALIS</jats:italic> ( <jats:italic>CEN</jats:italic> ) and the <jats:italic>Arabidopsis</jats:italic> gene <jats:italic>TERMINAL FLOWER 1</jats:italic> ( <jats:italic>TFL1</jats:italic> ) were shown to be homologous, which suggests that a common mechanism underlies indeterminacy in these plants. However, unlike <jats:italic>CEN</jats:italic> , <jats:italic>TFL1</jats:italic> is also expressed during the vegetative phase, where it delays the commitment to inflorescence development and thus affects the timing of the formation of the inflorescence meristem as well as its identity. </jats:p>

<jats:p>Regional brain activation was assessed by mapping of Fos-related protein expression in rats trained to self-administration of intravenous nicotine and cocaine. Both drugs produced specific overlapping patterns of activation in the shell and the core of the nucleus accumbens, medial prefrontal cortex, and medial caudate areas, but not in the amygdala. Thus, the reinforcing properties of cocaine and nicotine map on selected structures of the terminal fields of the mesocorticolimbic dopamine system, supporting the idea that common substrates for these addictive drugs exist.</jats:p>

<jats:p>Calnexin and calreticulin interact specifically with newly synthesized glycoproteins in the endoplasmic reticulum (ER) and function as molecular chaperones. The carbohydrate-specific interactions between ER components and glycoproteins synthesized in isolated canine pancreatic microsomes were analyzed using a cross-linking approach. A carbohydrate-dependent interaction between newly synthesized glycoproteins, the thiol-dependent reductase ERp57, and either calnexin or calreticulin was identified. The interaction between ERp57 and the newly synthesized glycoproteins required trimming of the N-linked oligosaccharide side chain. Thus, it is likely that ERp57 functions as part of the glycoprotein-specific quality control machinery operating in the lumen of the ER.</jats:p>

<jats:p>Numerous studies have revealed an association between nutritional status, adiposity, and reproductive maturity. The role of leptin, a hormone secreted from adipose tissue, in the onset of reproductive function was investigated. Normal prepubertal female mice injected with leptin grew at a slower rate than controls as a result of the hormone's thinning effects, but they reproduced up to 9 days earlier than controls and showed earlier maturation of the reproductive tract. These results suggest that leptin acts as a signal triggering puberty, thus supporting the hypothesis that fat accumulation enhances maturation of the reproductive tract.</jats:p>

<jats:p>Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-α (TNF-α). Moreover, TNF-α-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.</jats:p>