Retrieval of Context-Associated Memory is Dependent on the Cav3.2 T-Type Calcium Channel

Among all voltage-gated calcium channels, the T-type Ca2+ channels encoded by the Cav3.2 genes are highly expressed in the hippocampus, which is associated with contextual, temporal and spatial learning and memory. However, the specific involvement of the Cav3.2 T-type Ca2+ channel in these hippocampus-dependent types of learning and memory remains unclear. To investigate the functional role of this channel in learning and memory, we subjected Cav3.2 homozygous and heterozygous knockout mice and their wild-type littermates to hippocampus-dependent behavioral tasks, including trace fear conditioning, the Morris water-maze and passive avoidance. The Cav3.2 −/− mice performed normally in the Morris water-maze and auditory trace fear conditioning tasks but were impaired in the context-cued trace fear conditioning, step-down and step-through passive avoidance tasks. Furthermore, long-term potentiation (LTP) could be induced for 180 minutes in hippocampal slices of WTs and Cav3.2 +/− mice, whereas LTP persisted for only 120 minutes in Cav3.2 −/− mice. To determine whether the hippocampal formation is responsible for the impaired behavioral phenotypes, we next performed experiments to knock down local function of the Cav3.2 T-type Ca2+ channel in the hippocampus. Wild-type mice infused with mibefradil, a T-type channel blocker, exhibited similar behaviors as homozygous knockouts. Taken together, our results demonstrate that retrieval of context-associated memory is dependent on the Cav3.2 T-type Ca2+ channel

Practical Synthesis and Field Application of the Synthetic Sex Pheromone of Rice Stem Borer, Chilo suppressalis (Lepidoptera: Pyralidae)

Rice stem borer, Chilo suppressalis, is a common and major serious pest of rice, maize, and wheat crops across Asia, Europe, and Oceania countries. Its sex pheromone consists of three analogously compounds, i.e., (Z)-hexadec-11-enal (1), (Z)-octadec-13-enal (2), and (Z)-hexadec-9-enal (3), as long-chain aliphatic internal cis-alkenyl aldehydes. In order to perform an economic and widespread pest control management of rice stem borer, a versatile and efficient synthetic strategy is required. A versatile and efficient synthesis using a common synthetic route for cis-alkenals with high overall yields is described. Commercially available inexpensive aliphatic diols were chosen as starting materials. Two key steps were employed to synthesize the long-chain aliphatic internal cis-alkenes in excellent yields, including the alkylation of terminal alkynes without the utilization of a highly polar aprotic cosolvent and the versatile cis-selective semihydrogenation for the reduction of internal alkynes with excellent stereoselectivity. The results of field tests showed that the synthetic sex pheromone blend was highly effective for the capture of rice stem borer

Passive avoidance tests.

<p><b><i>A.</i></b> Step-through passive avoidance test. The latency of the mice entering the dark compartment was recorded 24 hours after the training session. The latency of the Ca_v3.2 ^−/− mice (KO −/−) was significantly shorter than that of the WT and the Ca_v3.2 ^+/− (KO +/−) mice. Asterisk indicates <i>p</i><0.01; numbers in parentheses indicate the number of animals used in this experiment. <b><i>B.</i></b> Step-down passive avoidance. The latency of the mice to step off the elevated platform onto the floor was recorded 24 hours after the training session. The latency of the Ca_v3.2 ^−/− (KO −/−) to step off the platform was significantly shorter than that of the WT and Ca_v3.2 ^+/− (KO +/−) mice. Asterisk indicates <i>p</i><0.05; numbers in parentheses indicate the number of animals used in this experiment.</p

Fear conditioning tests.

<p><b><i>A</i></b>. The freezing percentage during the acquisition stage of the trace fear conditioning. The freezing percentage increased in all groups during the three trials of the trace fear conditioning, indicating that the mice were learning. <b><i>B</i></b>. Contextual test. The freezing percentage for this test was significantly lower in the Ca_v3.2 ^−/− mice compared to the Ca_v3.2 ^+/− and WT mice 24 hours after the trace fear conditioning. Asterisk indicates <i>p</i><0.05. <b><i>C.</i></b> Tone test. For this test, no significant difference in the freezing percentage was observed between the Ca_v3.2 ^−/−, Ca_v3.2 ^+/− and WT 48 hours after the trace fear conditioning was groups. <b><i>D</i></b>. Extinction test. After the tone test, the mice were exposed to the same tone for 7 continuous days to test for extinction. The WT (in solid circle) and homozygous knockouts (in open triangle) showed similar extinction levels after 3 days, although they responded differently on the first two days. WT: wild-type; KO +/−: Ca_v3.2 ^+/−; KO −/−: Ca_v3.2 ^−/−.</p

Fear conditioning tests after mibefradil infusion.

<p><b><i>A</i></b>. Freezing behavior after mibefradil infusion. After infusion with mibefradil, all mice appeared well groomed and healthy in their home cages and exhibited normal freezing behaviors during training courses. <b><i>B</i></b><i>.</i> Context-cued trace fear memory test after infusion with mibefradil. The mice infused with mibefradil exhibited a significantly lower freezing percentage than the sham control. Asterisk indicates <i>p</i><0.05; numbers in parentheses indicate the number of animals used in this experiment. <b><i>C.</i></b> Auditory trace fear memory test after infusion with mibefradil. To test the trace fear memory of the tone, the mice infused with mibefradil or saline were placed into a chamber different from the one where they had received the trace fear conditioning and the same tone cue was given for 6 minutes without subsequent electrical foot shock. No significant difference was observed between the two groups. Numbers in parentheses indicate the number of animals used in this experiment.</p

JAK2 V617F Mutation in Adult Taiwanese Patients with Essential Thrombocythemia: More Prevalent in Old Patients and Correlated with Higher Hemoglobin Level and Higher Leukocyte Count

Background: Essential thrombocythemia (ET) is classified as a chronic myeloproliferative neoplasm. JAK2 V617F mutation is found in about 50–60% patients with ET. We aim to determine the prevalence of JAK2 V617F mutation and its association with phenotype in adult Taiwanese patients with ET. Methods: In this combined retrospective and prospective study, adult ET patients, at least 18 years of age, were enrolled between November 2007 and September 2011. Genomic DNA was extracted from unsorted bone marrow and/or peripheral blood samples for the detection of JAK2 V617F mutation by allele-specific polymerase chain reaction. The clinical and laboratory characteristics of all patients at the time of diagnosis or referral were determined retrospectively by chart review. Results: A total of 82 patients were enrolled, and JAK2 V617F mutation was detected in 55 patients (67.1%). JAK2 V617F mutation was significantly more prevalent in old patients (36.4% vs. 14.8%, p=0.044), and associated with higher hemoglobin level (median 13.7 vs. 12.8 g/dL p=0.012) and higher white blood cell count at diagnosis (12.1×103 vs. 8.8×103/μL p=0.015). ET patients with the mutation also tend to have lower platelet count (median 902×103 vs. 1078×103/μL p=0.051). In a binary logistic regression model, only higher hemoglobin concentration was significantly associated with JAK2 V617F mutational status (odds ratio 1.2 95% confidence interval 1.0–1.5; p=0.047). Conclusion: JAK2 V617F mutation in Taiwanese adult patients with ET has a high prevalence of 67.1% and is associated with old age, higher hemoglobin level, and higher leukocyte count