Contextual Fear Conditioning Is Associated With Lateralized Expression of the Immediate Early Gene c-fos in the Central and Basolateral Amygdalar Nuclei.

Fos, the protein product of the immediate early gene c-fos, was used to map functional circuitry underlying contextual conditioned fear. Male rats were given footshocks in a distinctive context and later tested using freezing as the behavioral measure and compared with no-shock and no-retention-test control groups. An increased number of Fos-immunoreactive neurons was found in the lateral part of the central nucleus and in the anterior basolateral and lateral amygdalar nuclei in the brains of the conditioned-fear group compared with controls. Further, a greater number of Fos-immunoreactive neurons was observed in the right central and anterior basolateral nuclei compared with the number of labeled neurons in these structures on the left. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ecological Neural Networks for Object Recognition and Generalization

Generalization is a critical capacity for organisms. Modeling the behavior of organisms with neural networks, some type of generalizations appear to be accessible to neural networks but other types do not. In this paper we present two simulations. In the first simulation we show that while neural networks can recognize where an object is located in the retina even if they have never experienced that object in that position ('where' generalization subtask), they have difficulty in recognizing the identity of a familiar object in a new position ('what' generalization subtask). In the second simulation we explore the hypothesis that organisms find another solution to the problem of recognizing objects in different positions on their retina: they move their eyes so that objects are always seen in the same position in the retina. This strategy emerges spontaneously in ecological neural networks that are allowed to move their 'eye' in order to bring different portions of the visible world in the central portion of their retina.     

Working Together Apart? Building a Knowledge‐Sharing Culture for Global Virtual Teams

A new impetus for greater knowledge‐sharing among team members needs to be emphasized due to the emergence of a significant new form of working known as ‘global virtual teams’. As information and communication technologies permeate every aspect of organizational life and impact the way teams communicate, work and structure relationships, global virtual teams require innovative communication and learning capabilities for different team members to effectively work together across cultural, organizational and geographical boundaries. Whereas information technology‐facilitated communication processes rely on technologically advanced systems to succeed, the ability to create a knowledge‐sharing culture within a global virtual team rests on the existence (and maintenance) of intra‐team respect, mutual trust, reciprocity and positive individual and group relationships. Thus, some of the inherent questions we address in our paper are: (1) what are the cross‐cultural challenges faced by global virtual teams?; (2) how do organizations develop a knowledge sharing culture to promote effective organizational learning among culturally‐diverse team members? and; (3) what are some of the practices that can help maximize the performance of global virtual teams? We conclude by examining ways that global virtual teams can be more effectively managed in order to reach their potential in this new interconnected world and put forward suggestions for further research.     

Multipurpose modular experimental station for the DiProI beamline of Fermi@Elettra free electron laser

We present a compact modular apparatus with a flexible design that will be operated at the DiProI beamline of the Fermi@Elettra free electron laser (FEL) for performing static and time-resolved coherent diffraction imaging experiments, taking advantage of the full coherence and variable polarization of the short seeded FEL pulses. The apparatus has been assembled and the potential of the experimental setup is demonstrated by commissioning tests with coherent synchrotron radiation. This multipurpose experimental station will be open to general users after installation at the Fermi@Elettra free electron laser in 2011.     

Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the pathogenesis and/or progression of several human diseases. Proteins are important molecular signposts of oxidative/nitrosative damage. However, it is generally unresolved whether the presence of oxidatively/nitrosatively modified proteins has a causal role or simply reflects secondary epiphenomena. Only direct identification and characterization of the modified protein(s) in a given pathophysiological condition can decipher the potential roles played by ROS/RNS-induced protein modifications. During the last few years, mass spectrometry (MS)-based technologies have contributed in a significant way to foster a better understanding of disease processes. The study of oxidative/nitrosative modifications, investigated by redox proteomics, is contributing to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities. MS-based technologies promise a contribution in a new era of molecular medicine, especially in the discovery of diagnostic biomarkers of oxidative/nitrosative stress, enabling early detection of diseases. Indeed, identification and characterization of oxidatively/nitrosatively modified proteins in human diseases has just begun.     

Competition Between Endogenous and Exogenous Orienting of Visual Attention.

The relation between reflexive and voluntary orienting of visual attention was investigated with 4 experiments: a simple detection task, a localization task, a saccade toward the target task, and a target identification task in which discrimination difficulty was manipulated. Endogenous and exogenous orienting cues were presented in each trial and their validity was manipulated orthogonally to examine whether attention mechanisms are mediated by separate systems and whether they have additive and independent effects on visual detection and discrimination. The results showed that each orienting mechanism developed its typical and independent effect in every case except for the difficult identification task. A theoretical framework for understanding the relationship between endogenous and exogenous orienting of attention is proposed, tested, and confirmed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Optimal bounds for the approximation of boolean functions and some applications

This paper presents an optimal bound on the Shannon function L(n,m,) that gives the worstcase circuit-size complexity to approximate, within an approximation degree at least , partial boolean functions having n inputs and domain size m. That is

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. Our bound applies to any partial boolean function and any approximation degree, and thus completes the study of boolean function approximation introduced by Pippenger (1977).

Our results give an upper bound for the hardness function h(ƒ), introduced by Nisan and Wigderson (1994), which denotes the minimum value l for which there exists a circuit of size at most l that approximates a boolean function ƒ with degree at least 1/l. Indeed, if H(n) denotes the maximum hardness value achieved by boolean functions with n inputs, we prove that for almost every nH(n)n/3 + n² + O(1). The exponent n/3 in the above inequality implies that no family of boolean functions exists which has ‘full’ hardness. This fact establishes connections with Allender and Strauss' (1994) work that explores the structure of BPP.

Finally, we show that for almost every n and for almost every boolean function ƒ of n inputs we have h(ƒ)2^{n/3−2 log n}. The contribution in the proof of the upper bound for L(n, m, ) can be viewed as a set of technical results that globally show how boolean linear operators are ‘well’ distributed on the class of 4-regular domains. This property is then applied to approximate partial boolean functions on general domains using a suitable composition of boolean linear operators.     

Identification of a Maturation Plasma Cell Index through a Highly Sensitive Droplet Digital PCR Assay Gene Expression Signature Validation in Newly Diagnosed Multiple Myeloma Patients

DNA microarrays and RNA-based sequencing approaches are considered important discovery tools in clinical medicine. However, cross-platform reproducibility studies undertaken so far have highlighted that microarrays are not able to accurately measure gene expression, particularly when they are expressed at low levels. Here, we consider the employment of a digital PCR assay (ddPCR) to validate a gene signature previously identified by gene expression profile. This signature included ten Hedgehog (HH) pathways’ genes able to stratify multiple myeloma (MM) patients according to their self-renewal status. Results show that the designed assay is able to validate gene expression data, both in a retrospective as well as in a prospective cohort. In addition, the plasma cells’ differentiation status determined by ddPCR was further confirmed by other techniques, such as flow cytometry, allowing the identification of patients with immature plasma cells’ phenotype (i.e., expressing CD19+/CD81+ markers) upregulating HH genes, as compared to others, whose plasma cells lose the expression of these markers and were more differentiated. To our knowledge, this is the first technical report of gene expression data validation by ddPCR instead of classical qPCR. This approach permitted the identification of a Maturation Index through the integration of molecular and phenotypic data, able to possibly define upfront the differentiation status of MM patients that would be clinically relevant in the future.     

The Interplay of Lung Cancer,COVID-19, and Vaccines

Patients with cancer are more susceptible to a higher risk of coronavirus infection and its severe complications than the general population. In addition, these patients were not included in the pivotal clinical trials for COVID-19 vaccines. Therefore, considerable uncertainty remains regarding the management of cancer patients during the COVID-19 pandemic and the safety of COVID-19 vaccinations in cancer patients. In this review, we summarize the current knowledge generated from the beginning of the COVID-19 pandemic on the vulnerability of cancer patients to the coronavirus disease, as well as the effectiveness of COVID-19 vaccines in this population. We also discuss the available data on the effects of anticancer treatment with immune checkpoint inhibitors on the immune responses to SARS-CoV-2 in cancer patients. Special attention in this review will be given to patients with lung cancer, as such patients are at an increased risk for severe effects from COVID-19.     

The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3

Proteins related to the ubiquitin-proteasome system play an important role during the differentiation and ciliogenesis of photoreceptor cells. Mutations in several genes involved in ubiquitination and proteostasis have been identified as causative of inherited retinal dystrophies (IRDs) and ciliopathies. USP48 is a deubiquitinating enzyme whose role in the retina is still unexplored although previous studies indicate its relevance for neurosensory organs. In this work, we describe that a pool of endogenous USP48 localises to the basal body in retinal cells and provide data that supports the function of USP48 in the photoreceptor cilium. We also demonstrate that USP48 interacts with the IRD-associated proteins ARL3 and UNC119a, and stabilise their protein levels using different mechanisms. Our results suggest that USP48 may act in the regulation/stabilisation of key ciliary proteins for photoreceptor function, in the modulation of intracellular protein transport, and in ciliary trafficking to the photoreceptor outer segment.