Locomotion occurs sporadically and needs to be started, maintained, and stopped. The neural substrate underlying the activation of locomotion is partly known, but little is known about mechanisms involved in termination of locomotion. Recently, reticulospinal neurons (stop cells) were found to play a crucial role in stopping locomotion in the lamprey: their activation halts ongoing locomotion and their inactivation slows down the termination process. Intracellular recordings of these cells revealed a distinct activity pattern, with a burst of action potentials at the beginning of a locomotor bout and one at the end (termination burst). The termination burst was shown to be time linked to the end of locomotion, but the mechanisms by which it is triggered have remained unknown. We studied this in larval sea lampreys (Petromyzon marinus; the sex of the animals was not taken into account). We found that the mesencephalic locomotor region (MLR), which is known to initiate and control locomotion, stops ongoing locomotion by providing synaptic inputs that trigger the termination burst in stop cells. When locomotion is elicited by MLR stimulation, a second MLR stimulation stops the locomotor bout if it is of lower intensity than the initial stimulation. This occurs for MLR-induced, sensory-evoked, and spontaneous locomotion. Furthermore, we show that glutamatergic and, most likely, monosynaptic projections from the MLR activate stop cells during locomotion. Therefore, activation of the MLR not only initiates locomotion, but can also control the end of a locomotor bout. These results provide new insights onto the neural mechanisms responsible for stopping locomotion.SIGNIFICANCE STATEMENT The mesencephalic locomotor region (MLR) is a brainstem region well known to initiate and control locomotion. Since its discovery in cats in the 1960s, the MLR has been identified in all vertebrate species tested from lampreys to humans. We now demonstrate that stimulation of the MLR not only activates locomotion, but can also stop it. This is achieved through a descending glutamatergic signal, most likely monosynaptic, from the MLR to the reticular formation that activates reticulospinal stop cells. Together, our findings have uncovered a neural mechanism for stopping locomotion and bring new insights into the function of the MLR.

Ibaraki virus (IBAV) is an arbovirus that is transmitted by biting midges and causes Ibaraki disease in cattle. IBAV induces apoptosis in several mammalian cell lines, and apoptosis in turn facilitates IBAV replication. In addition, virus-induced apoptosis may contribute to mammalian-specific pathogenicity considering that some arboviruses induce apoptosis in mammalian cells but not in insect cells. In this study, we found that when hamster lung cells (HmLu-1) are used as a virus host, IBAV causes severe cytopathic effects with little induction of apoptosis. Furthermore, pharmacological inhibition of apoptosis did not affect IBAV-induced cytotoxicity. These results indicate the existence of an apoptosis-independent pathway in which IBAV replicates and exerts cytotoxicity in mammalian cells.

Schmallenberg virus (SBV), discovered in 2011 in Germany, is associated with clinical manifestations of fever, diarrhea, reduced milk yield, abortions and congenital malformations in ruminants. Despite many studies performed for SBV, there is no detailed research on in vitro apoptotic effect of SBV. This study is aimed to determine apoptosis pathways and role of pro-apoptotic and anti-apoptotic molecules in Vero cells infected with SBV. The study results showed that SBV induced apoptosis via both extrinsic and intrinsic pathways by activating both caspase-8 and caspase-9, respectively. Expression analyses of pro-apoptotic (Bax, Bak and Puma) and anti-apoptotic (Bcl-2 and Bcl-XL) genes revealed that SBV-induced apoptosis causes upregulation of pro-apoptotic genes, dominantly via Puma gene, whereas Bcl-2 and Bcl-XL genes were downregulated. In conclusion, this is the first detailed report about SBV induced apoptosis in the Vero cells via both extrinsic and intrinsic cascades and apoptosis induction is seem to be regulated by Puma.

Figure-ground segregation is the process by which the visual system identifies image elements of figures and segregates them from the background. Previous studies examined figure-ground segregation in the visual cortex of monkeys where figures elicit stronger neuronal responses than backgrounds. It was demonstrated in anesthetized mice that neurons in the primary visual cortex (V1) of mice are sensitive to orientation contrast, but it is unknown whether mice can perceptually segregate figures from a background. Here, we examined figure-ground perception of mice and found that mice can detect figures defined by an orientation that differs from the background while the figure size, position or phase varied. Electrophysiological recordings in V1 of awake mice revealed that the responses elicited by figures were stronger than those elicited by the background and even stronger at the edge between figure and background. A figural response could even be evoked in the absence of a stimulus in the V1 receptive field. Current-source-density analysis suggested that the extra activity was caused by synaptic inputs into layer 2/3. We conclude that the neuronal mechanisms of figure-ground segregation in mice are similar to those in primates, enabling investigation with the powerful techniques for circuit analysis now available in mice.

Under homoeostatic conditions, the relationship between the coral Pocillopora damicornis and Vibrio coralliilyticus is commensal. An increase in temperature, or in the abundance of V. coralliilyticus, can turn this association pathogenic, causing tissue lysis, expulsion of the corals' symbiotic algae (genus Symbiodinium), and eventually coral death. Using a combination of microfluidics, fluorescence microscopy, stable isotopes, electron microscopy and NanoSIMS isotopic imaging, we provide insights into the onset and progression of V. coralliilyticus infection in the daytime and at night, at the tissue and (sub-)cellular level. The objective of our study was to connect the macro-scale behavioural response of the coral to the micro-scale nutritional interactions that occur between the host and its symbiont. In the daytime, polyps enhanced their mucus production, and actively spewed pathogens. Vibrio infection primarily resulted in the formation of tissue lesions in the coenosarc. NanoSIMS analysis revealed infection reduced 13C-assimilation in Symbiodinium, but increased 13C-assimilation in the host. In the night incubations, no mucus spewing was observed, and a mucus film was formed on the coral surface. Vibrio inoculation and infection at night showed reduced 13C-turnover in Symbiodinium, but did not impact host 13C-turnover. Our results show that both the nutritional interactions that occur between the two symbiotic partners and the behavioural response of the host organism play key roles in determining the progression and severity of host-pathogen interactions. More generally, our approach provides a new means of studying interactions (ranging from behavioural to metabolic scales) between partners involved in complex holobiont systems, under both homoeostatic and pathogenic conditions.

Removing the comb artifact introduced by imaging fibre bundles, or 'fibrescopes', for example in medical endoscopy, is essential to provide high quality images to the observer. Multispectral imaging (MSI) is an emerging method that combines morphological (spatial) and chemical (spectral) information in a single data 'cube'. When a fibrescope is coupled to a spectrally resolved detector array (SRDA) to perform MSI, comb removal is complicated by the demosaicking step required to reconstruct the multispectral data cube. To understand the potential for using SRDAs as multispectral imaging sensors in medical endoscopy, we assessed five comb correction methods with respect to five performance metrics relevant to biomedical imaging applications: processing time, resolution, smoothness, signal and the accuracy of spectral reconstruction. By assigning weights to each metric, which are determined by the particular imaging application, our results can be used to select the correction method to achieve best overall performance. In most cases, interpolation gave the best compromise between the different performance metrics when imaging using an SRDA.

Whether anatomic resection (AR) achieves better outcomes than nonanatomic resection (NAR) in patients with primary intrahepatic cholangiocarcinoma (ICC) is unclear. Data were retrieved for all consecutive patients who underwent liver resection for primary ICC from January 2007 to July 2017. The prognoses of the patients without direct invasion to contiguous organs or extrahepatic metastasis who underwent AR or NAR were compared. 85 patients underwent AR, and 65 patients underwent NAR. operation time were slightly decreased in the NAR group. The risk of Clavien-Dindo classification (CDC) IV in the AR group was significant higher than that in the NAR group. Cox regression analysis showed lymph node metastasis and adjuvant therapy were significant prognostic factors for overall survival (OS) and disease-free survival (DFS), respectively. After 1:1 propensity score matching (PSM), 29 pairs of patients were compared. The survival curves showed the NAR group had slightly improved DFS and OS than the AR group before and after matching. Thus, we conclude NAR was not inferior to AR in improving the survival outcomes for patients with primary solitary ICC lesions without direct invasion to contiguous organs or extrahepatic metastasis. Furthermore, patients may benefit from NAR.

Efficient gene delivery technologies play an essential role in the gene functional analyses that are necessary for basic and applied researches. Mosquitoes are ubiquitous insects, responsible for transmitting many deadly arboviruses causing millions of human deaths every year. The lack of efficient and flexible gene delivery strategies in mosquitoes are among the major hurdles for the study of mosquito biology and mosquito-pathogen interactions. We found that Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the type baculovirus species, can efficiently transduce mosquito cells without viral propagation, allowing high level gene expression upon inducement by suitable promoters without obvious negative effects on cell propagation and viability. AcMNPV transduces into several mosquito cell types, efficiently than in commonly used mammalian cell lines and classical plasmid DNA transfection approaches. We demonstrated the application of this system by expressing influenza virus neuraminidase (NA) into mosquito hosts. Moreover, AcMNPV can transduce both larvae and adults of essentially all blood-sucking mosquito genera, resulting in bright fluorescence in insect bodies with little or no tissue barriers. Our experiments establish baculovirus as a convenient and powerful gene delivery vector in vitro and in vivo that will greatly benefit research into mosquito gene regulation, development and the study of mosquito-borne viruses.

Pregnancy and motherhood are increasingly subjected to surveillance by medical professionals, the media, and the general public, and discourses of ideal parenting are propagated alongside an admonishment of the perceived "failing" maternal subject. However, despite this scrutiny, the mundane activities of parenting are often impervious to ethnographic forms of inquiry. Challenges for ethnographic researchers include the restrictions of becoming immersed in the private space of the home where parenting occurs and an institutional structure that discourages exploratory and long-term fieldwork. This paper draws on four studies, involving thirty-four participants, that explored their journeys into the space of parenthood and their everyday experiences. The studies all employed forms of visual ethnography, including artifacts, photo elicitation, timelines, collage, and sandboxing. The paper argues that visual methodologies can enable access to unseen aspects of parenting and engender forms of temporal extension, which can help researchers to disrupt the restrictions of tightly time bounded projects.

Activated Schwann cells put out cytoplasmic processes that play a significant role in cell migration and axon regeneration. Following nerve injury, axonal mitochondria release mitochondrial damage-associated molecular patterns (mtDAMPs), including formylated peptides and mitochondrial DNA (mtDNA). We hypothesize that mtDAMPs released from disintegrated axonal mitochondria may stimulate Schwann cells to put out cytoplasmic processes. We investigated RT4-D6P2T schwannoma cells (RT4) in vitro treated with N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) or cytosine-phospho-guanine oligodeoxynucleotide (CpG ODN) for 1, 6 and 24 h. We also used immunohistochemical detection to monitor the expression of formylpeptide receptor 2 (FPR2) and toll-like receptor 9 (TLR9), the canonical receptors for formylated peptides and mtDNA, in RT4 cells and Schwann cells distal to nerve injury. RT4 cells treated with fMLP put out a significantly higher number of cytoplasmic processes compared to control cells. Preincubation with PBP10, a selective inhibitor of FPR2 resulted in a significant reduction of cytoplasmic process outgrowth. A significantly higher number of cytoplasmic processes was also found after treatment with CpG ODN compared to control cells. Pretreatment with inhibitory ODN (INH ODN) resulted in a reduced number of cytoplasmic processes after subsequent treatment with CpG ODN only at 6 h, but 1 and 24 h treatment with CpG ODN demonstrated an additive effect of INH ODN on the development of cytoplasmic processes. Immunohistochemistry and western blot detected increased levels of tyrosine-phosphorylated paxillin in RT4 cells associated with cytoplasmic process outgrowth after fMLP or CpG ODN treatment. We found increased immunofluorescence of FPR2 and TLR9 in RT4 cells treated with fMLP or CpG ODN as well as in activated Schwann cells distal to the nerve injury. In addition, activated Schwann cells displayed FPR2 and TLR9 immunostaining close to GAP43-immunopositive regenerated axons and their growth cones after nerve crush. Increased FPR2 and TLR9 immunoreaction was associated with activation of p38 and NFkB, respectively. Surprisingly, the growth cones displayed also FPR2 and TLR9 immunostaining. These results present the first evidence that potential mtDAMPs may play a key role in the induction of Schwann cell processes. This reaction of Schwann cells can be mediated via FPR2 and TLR9 that are canonical receptors for formylated peptides and mtDNA. The possible role for FPR2 and TLR9 in growth cones is also discussed.

Effective and tolerable salvage therapies for elderly patients with chemorefractory acute myeloid leukemia (AML) are limited and usually do not change the poor clinical outcome. We recently described in several chemorefractory elderly AML patients that a novel biomodulatory treatment regimen consisting of low-dose azacitidine (AZA) in combination with PPARγ agonist pioglitazone (PGZ) and all-trans retinoic acid (ATRA) induced complete remission of leukemia and also triggered myeloid differentiation with rapid increase of peripheral blood neutrophils. Herein, we further investigated our observations and comprehensively analyzed cell differentiation in primary AML blasts after treatment with ATRA, AZA, and PGZ ex vivo. The drug combination was found to significantly inhibit cell growth as well as to induce cell differentiation in about half of primary AML blasts samples independent of leukemia subtype. Notably and in comparison to ATRA/AZA/PGZ triple-treatment, effects on cell growth and myeloid differentiation with ATRA monotherapy was much less efficient. Morphological signs of myeloid cell differentiation were further confirmed on a functional basis by demonstrating increased production of reactive oxygen species as well as enhanced phagocytic activity in AML blasts treated with ATRA/AZA/PGZ. In conclusion, we show that biomodulatory treatment with ATRA/AZA/PGZ can induce phenotypical and functional differentiation of primary AML blasts into neutrophil like cells, which aside from its antileukemic activity may lower neutropenia associated infection rates in elderly AML patients in vivo. Clinical impact of the ATRA/AZA/PGZ treatment regimen is currently further investigated in a randomized clinical trial in chemorefractory AML patients (NCT02942758).

TLQP-21 is a neuropeptide which has been implicated in regulation of nociception and other relevant physiologic functions. Although recent studies identified C3a and gC1q receptors as targets for TLQP-21, its intracellular molecular mechanisms of action remain largely unidentified. Our aim was (i) to explore the intracellular signaling pathway(s) activated by JMV5656, a novel derivative of TLQP-21, in RAW264.7 macrophages, and (ii) to assess linkages of these pathways with its purported receptors. JMV5656 stimulated, in a dose-dependent fashion, a rapid and transient increase in intracellular Ca2+ concentrations in RAW264.7 cells; repeated exposure to the peptide resulted in a lower response, suggesting a possible desensitization mechanism of the receptor. In particular, JMV5656 increased cytoplasmic Ca2+ levels by a PLC-dependent release of Ca2+ from the endoplasmic reticulum. STIM proteins and Orai Ca2+ channels were activated and played a crucial role. In fact, treatment of the cells with U73122 and thapsigargin modulated the increase of intracellular Ca2+ levels stimulated by JMV5656. Moreover, in RAW264.7 cells intracellular Ca2+ increases did not occur through the binding of JMV5656 to the C3a receptor, since the increase of intracellular Ca2+ levels induced by JMV5656 was not affected by specific siRNA against C3aR. In summary, our study provides new indications for the downstream effects of JMV5656 in macrophages, suggesting that it could activate receptors different from the C3aR.

Complex spatiotemporal non-linearity as observed during cardiac arrhythmia strongly correlates with vortex-like excitation wavelengths and tissue characteristics. Therefore, the control of arrhythmic patterns requires fundamental understanding of dependencies between onset and perpetuation of arrhythmia and substrate instabilities. Available treatments, such as drug application or high-energy electrical shocks, are discussed for potential side effects resulting in prognosis worsening due to the lack of specificity and spatiotemporal precision. In contrast, cardiac optogenetics relies on light sensitive ion channels stimulated to trigger excitation of cardiomyocytes solely making use of the inner cell mechanisms. This enables low-energy, non-damaging optical control of cardiac excitation with high resolution. Recently, the capability of optogenetic cardioversion was shown in Channelrhodopsin-2 (ChR2) transgenic mice. But these studies used mainly structured and local illumination for cardiac stimulation. In addition, since optogenetic and electrical stimulus work on different principles to control the electrical activity of cardiac tissue, a better understanding of the phenomena behind optogenetic cardioversion is still needed. The present study aims to investigate global illumination with regard to parameter characterization and its potential for cardioversion. Our results show that by tuning the light intensity without exceeding 1.10 mW mm-2, a single pulse in the range of 10-1,000 ms is sufficient to reliably reset the heart into sinus rhythm. The combination of our panoramic low-intensity photostimulation with optical mapping techniques visualized wave collision resulting in annihilation as well as propagation perturbations as mechanisms leading to optogenetic cardioversion, which seem to base on other processes than electrical defibrillation. This study contributes to the understanding of the roles played by epicardial illumination, pulse duration and light intensity in optogenetic cardioversion, which are the main variables influencing cardiac optogenetic control, highlighting the advantages and insights of global stimulation. Therefore, the presented results can be modules in the design of novel illumination technologies with specific energy requirements on the way toward tissue-protective defibrillation techniques.

No abstract available

Posttraumatic stress disorder (PTSD) is a trauma and stressor related disorder that may develop after exposure to an event that involved the actual or possible threat of death, violence or serious injury. Its molecular underpinning is still not clear. Brain-derived neurotrophic factor (BDNF) modulates neuronal processes such as the response to stress, but also weight control, energy and glucose homeostasis. Plasma BDNF levels and a functional BDNF Val66Met (rs6265) polymorphism were reported to be associated with PTSD, as well as with increased body mass index (BMI) and dyslipidaemia in healthy subjects and patients with cardio-metabolic diseases, but these results are controversial. The other frequently studied BDNF polymorphism, C270T (rs56164415), has been associated with the development of different neuropsychiatric symptoms/disorders. As far as we are aware, there are no data on the association of BDNF Val66Met and C270T polymorphisms with metabolic indices in PTSD. Due to high rates of obesity and dyslipidaemia in PTSD, the aim of this study was to elucidate the association of BDNF Val66Met and C270T polymorphisms with BMI and lipid levels in veterans with PTSD. We hypothesized that BDNF variants contribute to susceptibility to metabolic disturbances in PTSD. The study included 333 Caucasian males with combat related PTSD, diagnosed according to DSM-5 criteria. Genotyping of the BDNF Val66Met and C270T polymorphisms was performed using the real-time PCR method. Results were analyzed using hierarchical multiple linear regression and the Mann-Whitney test, with p-value corrected to 0.005. The results showed that BDNF Val66Met and BDNF C270T polymorphisms were not significantly associated with BMI, total cholesterol, LDL-cholesterol, HDL-cholesterol or triglycerides. Although the BDNF C270T polymorphism was nominally associated only with HDL-cholesterol in veterans with PTSD, this significance disappeared after controlling for the effect of age. Namely, slightly higher plasma HDL values in T allele carriers, compared to CC homozygotes, were associated with differences in age. Our results, controlled for the critical covariates, revealed that BDNF Val66Met and C270T were not significantly associated with metabolic indices in veterans with PTSD and that these genetic variants do not contribute to susceptibility to metabolic disturbances in PTSD.

Aims and Objectives: To facilitate individualized assessment of unresponsive patients in the intensive care unit for signs of preserved consciousness after acute brain injury. Background: Physicians and neuroscientists are increasingly recognizing a disturbing dilemma: Brain-injured patients who appear entirely unresponsive at the bedside may show signs of covert consciousness when examined by functional MRI (fMRI) or electroencephalography (EEG). According to a recent meta-analysis, roughly 15% of behaviorally unresponsive brain-injured patients can participate in mental tasks by modifying their brain activity during EEG- or fMRI-based paradigms, suggesting that they are conscious and misdiagnosed. This has major ethical and practical implications, including prognosis, treatment, resource allocation, and end-of-life decisions. However, EEG- or fMRI-based paradigms have so far typically been tested in chronic brain injury. Hence, as a novel approach, CONNECT-ME will import the full range of consciousness paradigms into neurocritical care. Methods: We will assess intensive care patients with acute brain injury for preserved consciousness by serial and multimodal evaluation using active, passive and resting state fMRI and EEG paradigms, as well as state-of-the-art clinical techniques including pupillometry and sophisticated clinical rating scales such as the Coma Recovery Scale-Revised. In addition, we are establishing a biobank (blood, cerebrospinal fluid and brain tissue, where available) to facilitate future genomic and microbiomic research to search for signatures of consciousness recovery. Discussion: We anticipate that this multimodal approach will add vital clinical information, including detection of preserved consciousness in patients previously thought of as unconscious, and improved (i.e., personalized) prognostication of individual patients. Our aim is two-fold: We wish to establish a cutting-edge tertiary care clinical service for unresponsive patients in the intensive care unit and lay the foundation for a fruitful multidisciplinary research environment for the study of consciousness in acute brain injury. Of note, CONNECT-ME will not only enhance our understanding of consciousness disorders in acute brain injury but it will also raise awareness for these patients who, for obvious reasons, have lacked a voice so far. Trial registration: The study is registered with clinicaltrials.org (ClinicalTrials.gov Identifier: NCT02644265).

Acinetobacter baumannii is one of the most important nosocomial pathogens, and thus it is required to investigate how it disseminate in hospitals and infect patients. We performed whole genome sequencing for 24 A. baumannii strains isolated successively from the blood of a single patient to evaluate whether repeated infections were due to re-infection or relapse infection and to investigate within-host evolution. The whole genome of the first strain, BL1, was sequenced de novo using the PacBio RSII system. BL2-BL24, were sequenced with an Illumina Hiseq4000 and mapped to the genome sequences of BL1. We identified 42 single-nucleotide variations among the strains. The SNVs differentiated the strains into three groups, BL1, BL2-BL16, and BL17-BL24, indicating that the patient suffered from re-infections or co-infections by similar, but different strains. The results also showed that A. baumannii strains in each group were rather stable at the genomic level. Our study emphasizes the importance of intensive infection control.

Natural killer (NK) cells are innate lymphocytes with a strong antitumor ability. In tumor patients, such as multiple myeloma (MM) patients, an elevated number of NK cells after stem cell transplantation (SCT) has been reported to be correlated with a higher overall survival rate. With the aim of improving NK cell use for adoptive cell therapy, we also addressed the cytotoxicity of patient-derived, cytokine-stimulated NK cells against MM cells at specific time points: at diagnosis and before and after autologous stem cell transplantation. Remarkably, after cytokine stimulation, the patients' NK cells did not significantly differ from those of healthy donors. In a small cohort of MM patients, we were able to isolate autologous tumor cells, and we could demonstrate that IL-2/15 stimulated autologous NK cells were able to significantly improve their killing capacity of autologous tumor cells. With the aim to further improve the NK cell killing capacity against MM cells, we investigated the potential use of NK specific check point inhibitors with focus on NKG2A because this inhibitory NK cell receptor was upregulated following ex vivo cytokine stimulation and MM cells showed HLA-E expression that could even be increased by exposure to IFN-γ. Importantly, blocking of NKG2A resulted in a significant increase in the NK cell-mediated lysis of different MM target cells. Finally, these results let suggest that combining cytokine induced NK cell activation and the specific check point inhibition of the NKG2A-mediated pathways can be an effective strategy to optimize NK cell therapeutic approaches for treatment of multiple myeloma.

Microglia are patrolling cells that sense changes in the brain microenvironment and respond acquiring distinct phenotypes that can be either beneficial or detrimental for brain homeostasis. Anti-inflammatory microglia release soluble factors that might promote brain repair; however, in glioma, anti-inflammatory microglia dampen immune response and promote a brain microenvironment that foster tumor growth and invasion. The chemokine CXCL16 is expressed in the brain, where it is neuroprotective against brain ischemia, and it has been found to be over-expressed in glioblastoma (GBM). Considering that CXCL16 specific receptor CXCR6 is diffusely expressed in the brain including in microglia cells, we wanted to investigate the role of CXCL16 in the modulation of microglia cell activity and phenotype, and in the progression of glioma. Here we report that CXCL16 drives microglia polarization toward an anti-inflammatory phenotype, also restraining microglia polarization toward an inflammatory phenotype upon LPS and IFNγ stimulation. In the context of glioma, we demonstrate that CXCL16 released by tumor cells is determinant in promoting glioma associated microglia/macrophages (GAMs) modulation toward an anti-inflammatory/pro-tumor phenotype, and that cxcr6ko mice, orthotopically implanted into the brain with GL261 glioma cells,survive longer compared to wild-type mice. We also describe that CXCL16/CXCR6 signaling acts directly on mouse glioma cells, as well as human primary GBM cells, promoting tumor cell growth, migration and invasion. All together these data suggest that CXCL16 signaling could represent a good target to modulate microglia phenotype in order to restrain inflammation or to limit glioma progression.

MicroRNAs (miRs) have been reported to serve critical roles in the progression of tumors. However, thus far, the role of miR-34a in breast cancer is largely unknown. Therefore, the present study aimed to investigate the expression and role of miR-34a in breast cancer, and to further explore the underlying molecular mechanism. Reverse transcription-quantitative polymerase chain reaction was performed to detect the level of miR-34a in human breast cancer tissues. In addition, the role of miR-34a in MCF-7 breast cancer cells was investigated by performing miR-34a overexpression or downregulation through transfection with miR-34a mimic or inhibitor, respectively. Next, the viability and invasion of the MCF-7 cells were respectively analyzed by MTT assay and transwell assay, while apoptosis and cell cycle progression were examined by flow cytometry. Furthermore, associated protein levels were measured using western blotting. The results demonstrated that miR-34a was downregulated in human breast cancer tissues in comparison with the adjacent normal tissues. In addition, Notch1 was demonstrated to be a direct target of miR-34a. miR-34a mimic transfection inhibited MCF-7 cell viability, induced cell apoptosis and G1 phase arrest, and prevented cell invasion, while miR-34a inhibitor transfection resulted in the opposite effects. In conclusion, the presented data indicated that miR-34a suppressed breast cancer cell proliferation and invasion, and its effect may partly be exerted by targeting Notch1.