Invariant visual representation by single neurons in the human brain

It takes a fraction of a second to recognize a person or an object even when seen under strikingly different conditions. How such a robust, high-level representation is achieved by neurons in the human brain is still unclear. In monkeys, neurons in the upper stages of the ventral visual pathway respond to complex images such as faces and objects and show some degree of invariance to metric properties such as the stimulus size, position and viewing angle. We have previously shown that neurons in the human medial temporal lobe (MTL) fire selectively to images of faces, animals, objects or scenes. Here we report on a remarkable subset of MTL neurons that are selectively activated by strikingly different pictures of given individuals, landmarks or objects and in some cases even by letter strings with their names. These results suggest an invariant, sparse and explicit code, which might be important in the transformation of complex visual percepts into long-term and more abstract memories.     

Correlation of ammonia liberation and calcium deposition by the avian egg and blood ammonia levels in the laying hen

Zusammenfassung Mittels biochemischer Daten wird der Nachweis erbracht, dass im Ovidukt des Huhnes während der Schalenbildung zwar vermehrt NH₄ ⁺ freigesetzt wird, jedoch eine negative Korrelation zwischen NH₄ ⁺-Produktion und Ca⁺⁺-Abscheidung besteht.

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Supported by a training grant from the U.S. Public Health Service No. 5-T1-DE-118. We thank Dr.P. R. Tramell for his help during the initial stage of this investigation.     

Circadian rhythmicity in phosphorylase activity and glycogen content in the heart muscle of the scorpion,Heterometrus fulvipes,C.L. Koch

Summary Maximal activity levels of phosphorylase A and AB at 20.00 h alternate with minimal levels at 08.00 h of the day, while the glycogen content exhibited a reverse trend in the heart of the scorpion,Heterometrus fulvipes.Acknowledgment. The authors thank Prof. K.S. Swami, for providing facilities. The financial assistance rendered by UGC (to VJ) and ICMR (to DCR) is gratefully acknowledged.     

Hepatopancreatic amylase activity as a function of warm-adaptation in a fresh-water field crab

Zusammenfassung Im Hepatopankreas der Krabben sind Fermentsysteme, die eine Wärmeadaptation besitzen. Diese lässt sich mit ähnlichen physiologischen Erscheinungen bei kaltblütigen Vertebraten vergleichen.     

Dial variations in the levels of blood glucose and hepatopancreatic glycogen in the slug,Laevicaulis alte (Ferussac 1821)

Summary InLaevicaulis alte maximal blood glucose level at 00.00 h alternates with minimal level at 12.00 h of the day, while hepatopancreatic glycogen showed an opposite trend. Variations in blood glucose levels are inversely proportional to the corresponding variations in hepatopancreatic glycogen content, while blood glucose level shoots up to a maximum, hepatopancreatic glycogen declines to a minimum and vice versa.Acknowledgment. The authors thank Prof. K.S. Swami for providing facilities. The financial assistance rendered by ICMR (DCR), UGC (VJ) and CSIR (KS), New Delhi, India is gratefully acknowledged.     

Hyperglycemic activity of crab and scorpion hormones in grasshopper (Poecilocerus pictus)

Summary Hyperglycemic hormones obtained from crab and scorpion both cause significant, dose-dependent elevations of hemolymph sugars in the grasshopperPoecilocerus pictus. These results suggest a highly conservative evolution of some mandibulate arthropod neuro-hormones.This work was supported by CSIR grant to PSR.     

Effect of the scorpion,Heterometrus fulvipes (C. Koch), venom on some enzyme systems in rat (albino) tissues

Summary Sublethal doses ofHeterometrus fulvipes venom decreased NADP-specific isocitrate dehydrogenase and malate dehydrogenase activity levels and increased NADP-specific glucose-6-phosphate dehydrogenase and alkaline phosphatase activity levels during a 48-h-period.Acknowledgments. D. V. thanks the Council of Scientific and Industrial Research, New Delhi, for awarding a Senior Research fellowship.     

Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation

Eukaryotic cells rely on a surveillance mechanism known as the spindle checkpoint to ensure accurate chromosome segregation. The spindle checkpoint prevents sister chromatids from separating until all kinetochores achieve bipolar attachments to the mitotic spindle. Checkpoint proteins tightly inhibit the anaphase-promoting complex (APC), a ubiquitin ligase required for chromosome segregation and progression to anaphase. Unattached kinetochores promote the binding of checkpoint proteins Mad2 and BubR1 to the APC-activator Cdc20, rendering it unable to activate APC. Once all kinetochores are properly attached, however, cells inactivate the checkpoint within minutes, allowing for the rapid and synchronous segregation of chromosomes. How cells switch from strong APC inhibition before kinetochore attachment to rapid APC activation once attachment is complete remains a mystery. Here we show that checkpoint inactivation is an energy-consuming process involving APC-dependent multi-ubiquitination. Multi-ubiquitination by APC leads to the dissociation of Mad2 and BubR1 from Cdc20, a process that is reversed by a Cdc20-directed de-ubiquitinating enzyme. The mutual regulation between checkpoint proteins and APC leaves the cell poised for rapid checkpoint inactivation and ensures that chromosome segregation promptly follows the completion of kinetochore attachment. In addition, our results suggest a mechanistic basis for how cancer cells can have a compromised spindle checkpoint without corresponding mutations in checkpoint genes.     

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.