Enhancing antibody affinity through experimental sampling of non-deleterious CDR mutations predicted by machine learning.

The application of machine learning (ML) models to optimize antibody affinity to an antigen is gaining prominence. Unfortunately, the small and biased nature of the publicly available antibody-antigen interaction datasets makes it challenging to build an ML model that can accurately predict binding affinity changes due to mutations (ΔΔG). Recognizing these inherent limitations, we reformulated the problem to ask whether an ML model capable of classifying deleterious vs non-deleterious mutations can guide antibody affinity maturation in a practical setting.

Significance testing of rank cross-correlations between autocorrelated time series with short-range dependence.

Statistical dependency measures such as Kendall's Tau or Spearman's Rho are frequently used to analyse the coherence between time series in environmental data analyses. Autocorrelation of the data can, however, result in spurious cross correlations if not accounted for. Here, we present the asymptotic distribution of the estimators of Spearman's Rho and Kendall's Tau, which can be used for statistical hypothesis testing of cross-correlations between autocorrelated observations.

A comprehensive atlas of perineuronal net distribution and colocalization with parvalbumin in the adult mouse brain.

Perineuronal nets (PNNs) surround specific neurons in the brain and are involved in various forms of plasticity and clinical conditions. However, our understanding of the PNN role in these phenomena is limited by the lack of highly quantitative maps of PNN distribution and association with specific cell types. Here, we present a comprehensive atlas of Wisteria floribunda agglutinin (WFA)-positive PNNs and colocalization with parvalbumin (PV) cells for over 600 regions of the adult mouse brain.

From pupil to the brain: New insights for studying cortical plasticity through pupillometry.

Pupil size variations have been associated with changes in brain activity patterns related with specific cognitive factors, such as arousal, attention, and mental effort. The locus coeruleus (LC), a key hub in the noradrenergic system of the brain, is considered to be a key regulator of cognitive control on pupil size, with changes in pupil diameter corresponding to the release of norepinephrine (NE). Advances in eye-tracking technology and open-source software have facilitated accurate pupil size measurement in various experimental settings, leading to increased interest in using pupillometry to track the nervous system activation state and as a potential biomarker for brain disorders.

Selective Disruption of Perineuronal Nets in Mice Lacking Crtl1 is Sufficient to Make Fear Memories Susceptible to Erasure.

The ability to store, retrieve, and extinguish memories of adverse experiences is an essential skill for animals' survival. The cellular and molecular factors that underlie such processes are only partially known. Using chondroitinase ABC treatment targeting chondroitin sulfate proteoglycans (CSPGs), previous studies showed that the maturation of the extracellular matrix makes fear memory resistant to deletion.

Behavioral impulsivity is associated with pupillary alterations and hyperactivity in CDKL5 mutant mice.

Cyclin-dependent kinase-like 5 (Cdkl5) deficiency disorder (CDD) is a severe neurodevelopmental condition caused by mutations in the X-linked Cdkl5 gene. CDD is characterized by early-onset seizures in the first month of life, intellectual disability, motor and social impairment. No effective treatment is currently available and medical management is only symptomatic and supportive.

Knowledge, attitude, and practice in oral cancer: A national survey on 150 dental hygienists.

Objective: The aim of this study is to explore knowledge, practice, and attitude on oral cancer (OC) among a cohort of Italian dental hygienists, in consideration of their role in the field of early diagnosis.

Materials And Methods: A cross-sectional study of 150 Italian dental hygienists was performed to assess the participant's knowledge, practice, and attitude on OC. Data were collected using a structured self-administered questionnaire (through Google Forms).

A comparative analysis of the relationship between flood experience and private flood mitigation behaviour in the regions of England.

There has been a move towards a more integrated approach to flood risk management, which includes a stronger focus on property level measures. However, in England the uptake of these measures remains low. Flood experience has been found to influence preparedness (i.

MEYE: Web App for Translational and Real-Time Pupillometry.

Pupil dynamics alterations have been found in patients affected by a variety of neuropsychiatric conditions, including autism. Studies in mouse models have used pupillometry for phenotypic assessment and as a proxy for arousal. Both in mice and humans, pupillometry is noninvasive and allows for longitudinal experiments supporting temporal specificity; however, its measure requires dedicated setups.

Selecting antidepressants according to a drug-by-environment interaction: A comparison of fluoxetine and minocycline effects in mice living either in enriched or stressful conditions.

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder. It has been recently proposed that these drugs, by enhancing neural plasticity, amplify the influences of the living conditions on mood. Consequently, SSRI outcome depends on the quality of the environment, improving symptomatology mainly in individuals living in favorable conditions.

Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines.

It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 ± 4 nm, PDI of 0.

Sociohydrology: Scientific Challenges in Addressing the Sustainable Development Goals.

The Sustainable Development Goals (SDGs) of the United Nations Agenda 2030 represent an ambitious blueprint to reduce inequalities globally and achieve a sustainable future for all mankind. Meeting the SDGs for water requires an integrated approach to managing and allocating water resources, by involving all actors and stakeholders, and considering how water resources link different sectors of society. To date, water management practice is dominated by technocratic, scenario-based approaches that may work well in the short term but can result in unintended consequences in the long term due to limited accounting of dynamic feedbacks between the natural, technical, and social dimensions of human-water systems.

Detecting Flood-Rich and Flood-Poor Periods in Annual Peak Discharges Across Europe.

This paper proposes a method from Scan statistics for identifying flood-rich and flood-poor periods (i.e., anomalies) in flood discharge records.

Current European flood-rich period exceptional compared with past 500 years.

There are concerns that recent climate change is altering the frequency and magnitude of river floods in an unprecedented way. Historical studies have identified flood-rich periods in the past half millennium in various regions of Europe. However, because of the low temporal resolution of existing datasets and the relatively low number of series, it has remained unclear whether Europe is currently in a flood-rich period from a long-term perspective.

Changing climate both increases and decreases European river floods.

Climate change has led to concerns about increasing river floods resulting from the greater water-holding capacity of a warmer atmosphere. These concerns are reinforced by evidence of increasing economic losses associated with flooding in many parts of the world, including Europe. Any changes in river floods would have lasting implications for the design of flood protection measures and flood risk zoning.

Causative classification of river flood events.

A wide variety of processes controls the time of occurrence, duration, extent, and severity of river floods. Classifying flood events by their causative processes may assist in enhancing the accuracy of local and regional flood frequency estimates and support the detection and interpretation of any changes in flood occurrence and magnitudes. This paper provides a critical review of existing causative classifications of instrumental and preinstrumental series of flood events, discusses their validity and applications, and identifies opportunities for moving toward more comprehensive approaches.

Interplay between inflammation and neural plasticity: Both immune activation and suppression impair LTP and BDNF expression.

An increasing number of studies show that both inflammation and neural plasticity act as key players in the vulnerability and recovery from psychiatric disorders and neurodegenerative diseases. However, the interplay between these two players has been limitedly explored. In fact, while a few studies reported an immune activation, others conveyed an immune suppression, associated with an impairment in neural plasticity.

The Value of Empirical Data for Estimating the Parameters of a Sociohydrological Flood Risk Model.

In this paper, empirical data are used to estimate the parameters of a sociohydrological flood risk model. The proposed model, which describes the interactions between floods, settlement density, awareness, preparedness, and flood loss, is based on the literature. Data for the case study of Dresden, Germany, over a period of 200 years, are used to estimate the model parameters through Bayesian inference.

Combined Fluoxetine and Metformin Treatment Potentiates Antidepressant Efficacy Increasing IGF2 Expression in the Dorsal Hippocampus.

An increasing number of studies show that selective serotonin reuptake inhibitors (SSRIs) exert their therapeutic action, at least in part, by amplifying the influence of the living environment on mood. As a consequence, when administered in a favorable environment, SSRIs lead to a reduction of symptoms, but in stressful conditions, they show limited efficacy. Therefore, novel therapeutic approaches able to neutralize the influence of the stressful environment on treatment are needed.

Predicting antidepressant treatment outcome based on socioeconomic status and citalopram dose.

Selective serotonin reuptake inhibitors (SSRIs), the most prescribed antidepressant drugs, have incomplete efficacy and no clear mechanism of action. In addition, no reliable methods to identify patients who will benefit from treatment is available. In this study, we show that citalopram, a commonly used SSRI, produces a dose-dependent amplification of the influence of the environment on mood, making the severity of symptoms dependent on the level of socioeconomic status (SES).

Land use change impacts on floods at the catchment scale: Challenges and opportunities for future research.

Research gaps in understanding flood changes at the catchment scale caused by changes in forest management, agricultural practices, artificial drainage, and terracing are identified. Potential strategies in addressing these gaps are proposed, such as complex systems approaches to link processes across time scales, long-term experiments on physical-chemical-biological process interactions, and a focus on connectivity and patterns across spatial scales. It is suggested that these strategies will stimulate new research that coherently addresses the issues across hydrology, soil and agricultural sciences, forest engineering, forest ecology, and geomorphology.

Changing climate shifts timing of European floods.

A warming climate is expected to have an impact on the magnitude and timing of river floods; however, no consistent large-scale climate change signal in observed flood magnitudes has been identified so far. We analyzed the timing of river floods in Europe over the past five decades, using a pan-European database from 4262 observational hydrometric stations, and found clear patterns of change in flood timing. Warmer temperatures have led to earlier spring snowmelt floods throughout northeastern Europe; delayed winter storms associated with polar warming have led to later winter floods around the North Sea and some sectors of the Mediterranean coast; and earlier soil moisture maxima have led to earlier winter floods in western Europe.

Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study.

Selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressant drugs, have a variable and incomplete efficacy. In order to better understand SSRI action, we explored the hypothesis that SSRIs do not affect mood per se but amplify the influence of the living conditions on mood. To this aim, we exploited the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set, selected a subpopulation of 591 patients with an overlapping clinical history and analyzed treatment outcome according to dosage -20 or 40 mg per day of citalopram.

Fragmented patterns of flood change across the United States.

Trends in the peak magnitude, frequency, duration, and volume of frequent floods (floods occurring at an average of two events per year relative to a base period) across the United States show large changes; however, few trends are found to be statistically significant. The multidimensional behavior of flood change across the United States can be described by four distinct groups, with streamgages experiencing (1) minimal change, (2) increasing frequency, (3) decreasing frequency, or (4) increases in all flood properties. Yet group membership shows only weak geographic cohesion.