wimp, a dominant maternal-effect mutation, reduces transcription of a specific subset of segmentation genes in Drosophila.

BACKGROUND Italy has been one of the first western countries seriously involved in the COVID-19 pandemic in the first months of 2020 and so that the national government was forced to impose a long lockdown period, stopping all the people aggregation outdoor and indoor activities. From a social point of view this period of domestic confinement resulted in deep changes of behaviours and lifestyles, promoting in many people the onset of psychological symptoms and signs (including anxiety, depression, insomnia, and irritability among others) already known as associated with drug and alcohol abuse OBJECTIVE this study aims to assess the variation of alcohol drinking habits in a sample of Italian citizens during the COVID-19 lockdown and to identify the psychosocial factors surrounding it, in order to assess the specific subset of the population that could need psychosocial support during these events METHODS An online anonymous questionnaire was created and submitted from 9th April 2020 to 28th April 2020 using social medias and e-mails. Questions were related to personal details such as age, work, instruction, and, moreover, to alcohol drinking habits during the lockdown, including Alcohol Use Disorders Identification Test (AUDIT C) test questions RESULTS A total of 1234 surveys were filled out by subjects with an age range from 18 to 80 years old. An increase in both anxiety and fear has been detected in most of the participants (63% and 61% respectively) with a direct (r=0.652; p<0.001) relationship between them. Participants older than 50 years showed the strongest correlation between alcohol consumption, fear, and anxiety, (r=0.830, P <0.001 and r=0.741, P<0.001, respectively). Subjects living alone experienced a stronger association between anxiety, fear, and higher level of alcohol consumption (r: 0.529; P<0.001; r: 0.628, P<0.001 respectively). Moreover, 18% of participants increased alcohol consumption drinking during the lockdown. These subjects showed a lower frequency of alcohol consumption before the lockdown in comparison to the rest of the study population (2.5±0.96 vs 3±1.03, P<0.0001 respectively). Moreover, comparing the abovementioned groups, the percentage of subjects who experienced higher alcohol assumption before the 11th of March was higher in those that didn't change their drinking behaviour during the lockdown in comparison to that portion of them that experienced a worsening of alcohol abuse (r: 30.422, P<0.0001) CONCLUSIONS according to these data, during the Italian lockdown due to COVID 19 pandemic, different kind of people experienced an increase in alcohol drinking. Several psychosocial factors are involved in determining the increase in harmful alcohol consumption during this extraordinary stressful event and they must be addressed by the healthcare support in order to avoid awful lockdown impact on human life

Download Full-text

Maternal-effect lethal mutations on linkage group II of Caenorhabditis elegans.

Genetics ◽

10.1093/genetics/120.4.977 ◽

1988 ◽

Vol 120 (4) ◽

pp. 977-986

Author(s):

K J Kemphues ◽

M Kusch ◽

N Wolf

Keyword(s):

Caenorhabditis Elegans ◽

Linkage Group ◽

Maternal Effect ◽

Essential Genes ◽

The Other ◽

C Elegans ◽

Lethal Mutations ◽

Embryonic Lethal ◽

Embryonic Lethal Mutations ◽

F1 Progeny

Abstract We have analyzed a set of linkage group (LG) II maternal-effect lethal mutations in Caenorhabditis elegans isolated by a new screening procedure. Screens of 12,455 F1 progeny from mutagenized adults resulted in the recovery of 54 maternal-effect lethal mutations identifying 29 genes. Of the 54 mutations, 39 are strict maternal-effect mutations defining 17 genes. These 17 genes fall into two classes distinguished by frequency of mutation to strict maternal-effect lethality. The smaller class, comprised of four genes, mutated to strict maternal-effect lethality at a frequency close to 5 X 10(-4), a rate typical of essential genes in C. elegans. Two of these genes are expressed during oogenesis and required exclusively for embryogenesis (pure maternal genes), one appears to be required specifically for meiosis, and the fourth has a more complex pattern of expression. The other 13 genes were represented by only one or two strict maternal alleles each. Two of these are identical genes previously identified by nonmaternal embryonic lethal mutations. We interpret our results to mean that although many C. elegans genes can mutate to strict maternal-effect lethality, most genes mutate to that phenotype rarely. Pure maternal genes, however, are among a smaller class of genes that mutate to maternal-effect lethality at typical rates. If our interpretation is correct, we are near saturation for pure maternal genes in the region of LG II balanced by mnC1. We conclude that the number of pure maternal genes in C. elegans is small, being probably not much higher than 12.

Download Full-text

The Mutation masculinizer (man) Defines a Sex-Determining Gene With Maternal and Zygotic Functions in Musca domestica L.

Genetics ◽

10.1093/genetics/145.1.173 ◽

1997 ◽

Vol 145 (1) ◽

pp. 173-183 ◽

Cited By ~ 1

Author(s):

R Schmidt ◽

M Hediger ◽

R Nöthiger ◽

A Dübendorfer

Keyword(s):

Musca Domestica ◽

Maternal Effect ◽

Dominant Factor ◽

Loss Of Function ◽

New Mutation ◽

Yolk Proteins ◽

Hypomorphic Allele ◽

Internal Structures ◽

Primary Signal ◽

Pole Cells

In Musca domestica, the primary signal for sex determination is the dominant factor M, which is assumed to regulate a postulated female-determining gene F. Presence of M prevents expression of F so that male development ensues. In the absence of M, F can become active, which dictates the female pathway. The existence of F is inferred from FD, a dominant factor that is epistatic to M. We describe a new mutation masculinizer, which has all the properties expected for a null or strongly hypomorphic allele of F: (1) it maps to the same chromosomal location as FD, (2) homozygous man/man animals develop as males, (3) homozygous man/man clones generated in man/+ female larvae differentiate male structures, (4) man has a sex-determining maternal effect. About a third of the morphological males synthesize yolk proteins, which indicates that they are intersexual in internal structures. The maternal effect of man is complete in offspring that derive from homozygous man/man pole cells transplanted into female hosts. In this case, all man/+ progeny become fertile males that do not produce yolk proteins. A sex-determining maternal effect has previously been demonstrated for FD. Like F, maternal man + is needed for zygotic man + to become active, providing further evidence that man is a loss-of-function allele of F.

Download Full-text

Marcatori conclusivi del discorso diretto in italiano antico

Romanistisches Jahrbuch ◽

10.1515/roja-2019-0004 ◽

2019 ◽

Vol 70 (1) ◽

pp. 105-122

Author(s):

Davide Mastrantonio

Keyword(s):

Word Reading ◽

Old French ◽

Spoken Word ◽

Text Segmentation ◽

Direct Speech ◽

Unequal Distribution ◽

Specific Subset ◽

Ancient Texts

Abstract In this paper we deal with a specific subset of direct speech markers, to which little or no attention has been given so far: the expressions which codify the ending of the direct speech (“marcatori conclusivi del discorso diretto”). We analyse these markers in Old Italian texts, comparing them with their Latin and, in some cases, Old French equivalents. In the introduction (§1), we take into account various general issues related to ancient texts, namely the practice of spoken-word reading and the lack of systematic punctuation marking that helps text segmentation. After that (§2), we classify the different strategies ancient writers had at their disposal to signal that a direct speech is over, hence that what follows has to be interpreted as the narrator voice; the markers are organized in a range from most explicit to most implicit (disse > quando ebbe detto > a queste parole > allora > [Ø]). Thereafter (§3), we focus on two specific markers, the participial marker (detto questo) and the “connector + finite tense” marker (quando ebbe detto questo) in a corpus of nine texts. Though these two markers are roughly synonymic, their occurrence is not uniform among the analysed texts. The explanation of their unequal distribution is that they belong to different discourse traditions (Diskurstraditionen): “quando + finite tense” is a typical expression attested in Romance narrations (the so-called “quand-Satz”), whereas detto questo appears to be dependent on Latin tradition.

Download Full-text

Chemotherapy-Induced Survivin Regulation in Acute Myeloid Leukemia Cells

Applied Sciences ◽

10.3390/app11010460 ◽

2021 ◽

Vol 11 (1) ◽

pp. 460

Author(s):

Petra Otevřelová ◽

Barbora Brodská

Keyword(s):

Acute Myeloid Leukemia ◽

Cell Lines ◽

Myeloid Leukemia ◽

Survivin Expression ◽

Mitotic Cell ◽

Specific Subset ◽

Suitable Target ◽

Acute Myeloid Leukemia Cells ◽

Almost All ◽

Acute Myeloid

Survivin is a 16.5 kDa protein highly expressed in centrosomes, where it controls proper sister chromatid separation. In addition to its function in mitosis, survivin is also involved in apoptosis. Overexpression of survivin in many cancer types makes it a suitable target for cancer therapy. Western blotting and confocal microscopy were used to characterize the effect of chemotherapy on acute myeloid leukemia (AML) cells. We found enhanced survivin expression in a panel of AML cell lines treated with cytarabine (Ara-C), which is part of a first-line induction regimen for AML therapy. Simultaneously, Ara-C caused growth arrest and depletion of the mitotic cell fraction. Subsequently, the effect of a second component of standard therapy protocol, idarubicin, and of a known survivin inhibitor, YM-155, on cell viability and survivin expression and localization in AML cells was investigated. Idarubicin reversed Ara-C-induced survivin upregulation in the majority of AML cell lines. YM-155 caused survivin deregulation together with a viability decrease in cells resistant to idarubicin treatment, suggesting that YM-155 might be efficient in a specific subset of AML patients. Expression levels of other apoptosis-related proteins, in particular X-linked inhibitor of apoptosis (XIAP), Mcl-1, and p53, and of the cell-cycle inhibitor p21 considerably changed in almost all cases, confirming the off-target effects of YM-155.

Download Full-text

A neuronal ensemble encoding adaptive choice during sensory conflict in Drosophila

Nature Communications ◽

10.1038/s41467-021-24423-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Preeti F. Sareen ◽

Li Yan McCurdy ◽

Michael N. Nitabach

Keyword(s):

Food Choice ◽

Internal State ◽

Relevant Information ◽

Food Choices ◽

Small Population ◽

Sensory Conflict ◽

Shaped Body ◽

Motor Circuits ◽

Specific Subset ◽

Adaptive Choice

AbstractFeeding decisions are fundamental to survival, and decision making is often disrupted in disease. Here, we show that neural activity in a small population of neurons projecting to the fan-shaped body higher-order central brain region of Drosophila represents food choice during sensory conflict. We found that food deprived flies made tradeoffs between appetitive and aversive values of food. We identified an upstream neuropeptidergic and dopaminergic network that relays internal state and other decision-relevant information to a specific subset of fan-shaped body neurons. These neurons were strongly inhibited by the taste of the rejected food choice, suggesting that they encode behavioral food choice. Our findings reveal that fan-shaped body taste responses to food choices are determined not only by taste quality, but also by previous experience (including choice outcome) and hunger state, which are integrated in the fan-shaped body to encode the decision before relay to downstream motor circuits for behavioral implementation.

Download Full-text

513 CD26 enzymatic activity modulates efficient migration of adoptively transferred T cells to solid tumors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0513 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A549-A549

Author(s):

Megan Wyatt ◽

Stefanie Bailey ◽

Michelle Nelson ◽

Hannah Knochelmann ◽

Aubrey Smith ◽

...

Keyword(s):

T Cells ◽

Enzymatic Activity ◽

Solid Tumors ◽

Study Endpoint ◽

Melanoma Tumor ◽

Antitumor Response ◽

Migration Assay ◽

Specific Subset ◽

Donor Cells

BackgroundThe inadequate ability of adoptively transferred T cells to eradicate solid tumors limits their use in treatments for patients afflicted with those cancers. Efforts to improve ACT for solid tumors aim to identify strategies that poise T cells for optimal response. We have previously identified a specific subset of CD4 T cells which express high levels of the ubiquitous ectoenzyme dipeptidyl peptidase-4 (DPP-4), also known as CD26, that produce a tremendous antitumor response in solid tumor models. We therefore sought to investigate the importance of CD26 on T cells destined for ACT.MethodsWe adoptively transferred tumor specific CD26+ T cells into melanoma tumor-bearing CD26-/- mice, and continuously blocked the CD26 enzymatic activity of the donor cells in vivo with sitagliptin, an established competitive inhibitor of CD26.ResultsTumors in sitagliptin-treated mice eventually reached study endpoint, while tumors untreated mice were regressed for 130+ days. Tumor infiltration of donor cells and host CD8 and CD4 cells was diminished with sitagliptin treatment. A 32-plex cytokine array of blood plasma revealed a diminished profile of cytokines and chemokines, indicating that the inflammatory response of the T cells was dampened with sitagliptin treatment. Further experiments characterized the ability of CD26+ T cells to respond to tumor trafficking signals with a transwell migration assay and found that sitagliptin treatment significantly impaired their migratory capacity. However, sitagliptin did not impair the ability of T cells to functionally respond to antigen.ConclusionsThese data suggest that the enzymatic activity of CD26 is important for the ability of T cells to migrate to the tumor site in order to mount an effective antitumor response. Further investigations into the mechanism behind the role of CD26 are ongoing.Ethics ApprovalThis study was approved by the Medical University of South Carolina’s IACUC, protocol #00488

Download Full-text