Search

Primary frontal sinus Non-Hodgkin's lymphoma (NHL) is an extremely rare condition with 20 cases published in the existing literature to date. We describe a 64-year-old patient who presented with right orbital pain, severe headache and diplopia. He was initially diagnosed with acute exacerbation of chronic rhinosinusitis and responded well to antibiotic treatment, but his symptoms returned. The diagnosis of frontal sinus NHL was made only after functional endoscopic frontal sinus surgery was performed in general anaesthesia. A tumor mass, which was filling the entire right frontal sinus, was completely removed and sent to histopathological examination. The patient was finally diagnosed with diffuse large B-cell lymphoma of the frontal sinus and referred to the haematology department for tumor staging and chemotherapy. This case emphasizes the importance of early clinical suspicion and diagnosis, which leads to early treatment and better prognosis.

The biological basis of male-female brain differences has been difficult to elucidate in humans. The most striking morphological difference is size, with males having on average a larger brain than females( 1,2 ), yet a mechanistic understanding of how this difference arises remains to be elucidated. Here, we use brain organoids( 3 ) to demonstrate that while sex chromosomal complement has no observable effect on neurogenesis, sex steroids, namely androgens, lead to increased proliferation of cortical progenitors and an increased neurogenic pool. Transcriptomic analysis and functional studies demonstrate downstream effects on HDAC activity and mTOR pathway. Finally, we show that androgens specifically increase neurogenic output of excitatory neuronal progenitors, while inhibitory neuronal progenitors are not increased. These findings uncover a hitherto unknown role for androgens in regulating excitatory neuron number and represent a first step towards understanding the origin of human sex-related brain differences.

Objectives: Systemic steroids are the most common first-line therapy in sudden sensorineural hearing loss (SSNHL), with significant improvement in hearing outcomes in over 60% of patients. It is unknown why 40% of patients do not respond to systemic steroid therapy. Salvage treatment includes intratympanic steroids (ITS) and hyperbaric oxygenation (HBO) therapy, with inconsistent results reported. This study aimed to compare the results of ITS and HBO therapy in patients with SSNHL that previously failed systemic steroid therapy. Design: This is a comparative retrospective nonrandomized interventional cohort study, enrolling 126 patients with SSNHL. Out of these, 35 patients received HBO therapy, 43 patients received ITS, and 48 patients did not receive any second-line therapy (control group). Pure-tone audiograms were performed before and after the salvage therapy in the IT and HBO groups and at the same time interval in the control group. Study variables included age, time until therapy initiation, tinnitus status, and hearing outcomes, with a cutoff criteria of cumulative >30 dB improvement on all frequencies indicating recovery. Results: ITS and HBO therapy were associated with statistically significant hearing recovery at all frequencies compared to systemic steroids. The results show an average hearing improvement of 13.6 dB overall frequencies (250 to 8000 Hz) after ITS therapy and 7.4 dB in HBO therapy in comparison to the control group. Presence of significant hearing improvement positively correlated with age, ITS therapy, and HBO therapy. Presence of tinnitus before therapy was negatively correlated with hearing improvement. Patients with tinnitus present at the start of therapy improve 4.67 dB less on average compared to those without tinnitus. ITS therapy significantly reduced tinnitus compared to the other two treatment options. Patients with tinnitus present before therapy significantly improve hearing at low frequencies, compared to the control group. Conclusions: ITS and HBO therapy show superior hearing results compared to observation alone after failed oral steroid therapy for SSNHL. ITS shows an additional positive impact on tinnitus reduction and shows superior hearing outcomes after salvage therapy.

Placental infections are a major worldwide burden, particularly in developing countries. The placenta is a transient tissue located at the interface between the mother and the fetus. Some pathogens can access the placental barrier resulting in pathological transmission from mother to fetus, which may have a profound impact on the health of the developing fetus. Limited tissue accessibility, critical differences between humans and mice, and, until recently, lack of properin vitromodels, have hampered our understanding of the early placental response to pathogens. Here we use single-cell transcriptomics to describe the placental primary defence mechanisms against three pathogens that are known to cause fetal and maternal complications during pregnancy -Plasmodium falciparum, Listeria monocytogenesandToxoplasma gondii. We optimiseex vivoplacental explants of the first-trimester human placenta and show that trophoblasts (the epithelial-like cells of the placenta), and Hofbauer cells (placental macrophages) orchestrate a coordinated inflammatory response after 24 hours of infection. We show that hormone biosynthesis and transport are downregulated in the trophoblasts, suggesting that protective responses are promoted at the expense of decreasing other critical functions of the placenta, such as the endocrine production and the nourishment of the fetus. In addition, we pinpoint pathogen-specific effects in some placental lineages, including a strong mitochondrial alteration in the Hofbauer cells in response toT. gondii. Finally, we identify adaptive strategies and validate nutrient acquisition employed by theP. falciparumduring placental malaria infection. This study provides the first detailed cellular map of the first-trimester placenta upon infection and describes the early events that may lead to fetal and placental disorders if left unchecked.

Researchers are exploring sex differences in experimental models of both development and disease—but are we doing enough? In this collection of Voices, we celebrate researchers who are asking this question and starting to offer mechanistic clues on sexually dimorphic differences seen in interorgan communication, metabolic disease, neurological disorders, and more.

We thank the Cellular Genetics wet lab support team, Cellular Genetics IT team, Sanger Sequencing operations and Sanger Cytometry Core facility for their essential help. We thank the Gene Editing team for providing iPSC knock-out lines. We would also like to thank Ruxandra Tesloianu and Luz Garcia-Alonso for their help setting up the scATAC-seq computational analysis. We thank Jana Eliasova for her help with figure design and Christina Usher and Aidan Maartens for their edits in the text. This work was mainly funded by the Open Targets consortium (OTAR026 and OTAR032 project) and the Wellcome Sanger core funding (WT206194) with additional support from Open Targets projects OTAR037, OTAR2065, OTAR2071. The authors are grateful to the funders for their support and additional care given to their members during the COVID-19 pandemic. D.A.-E. thanks CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. This study makes use of cell lines and data generated by the HiPSci Consortium, funded by The Wellcome Trust and the MRC (Medical Research Council). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This publication is part of the Human Cell Atlas- www.humancellatlas.org/publications. We thank the Cellular Genetics wet lab support team, Cellular Genetics IT team, Sanger Sequencing operations and Sanger Cytometry Core facility for their essential help. We thank the Gene Editing team for providing iPSC knock-out lines. We would also like to thank Ruxandra Tesloianu and Luz Garcia-Alonso for their help setting up the scATAC-seq computational analysis. We thank Jana Eliasova for her help with figure design and Christina Usher and Aidan Maartens for their edits in the text. This work was mainly funded by the Open Targets consortium (OTAR026 and OTAR032 project) and the Wellcome Sanger core funding (WT206194) with additional support from Open Targets projects OTAR037, OTAR2065, OTAR2071. The authors are grateful to the funders for their support and additional care given to their members during the COVID-19 pandemic. D.A.-E. thanks CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. This study makes use of cell lines and data generated by the HiPSci Consortium, funded by The Wellcome Trust and the MRC (Medical Research Council). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This publication is part of the Human Cell Atlas-www.humancellatlas.org/publications. Myeloid cells are central to homeostasis and immunity. Characterising in vitro myelopoiesis protocols is imperative for their use in research, immunotherapies, and understanding human myelopoiesis. Here, we generate a >470K cells molecular map of human induced pluripotent stem cells (iPSC) differentiation into macrophages. Integration with in vivo single-cell atlases shows in vitro differentiation recapitulates features of yolk sac hematopoiesis, before definitive hematopoietic stem cells (HSC) emerge. The diversity of myeloid cells generated, including mast cells and monocytes, suggests that HSC-independent hematopoiesis can produce multiple myeloid lineages. We uncover poorly described myeloid progenitors and conservation between in vivo and in vitro regulatory programs. Additionally, we develop a protocol to produce iPSC-derived dendritic cells (DC) resembling cDC2. Using CRISPR/Cas9 knock-outs, we validate the effects of key transcription factors in macrophage and DC ontogeny. This roadmap of myeloid differentiation is an important resource for investigating human fetal hematopoiesis and new therapeutic opportunities.

Simultana bilateralna kohlearna implantacija kod djece izvodi se zbog prednosti binauralnog slušanja i bolje kvalitete života u odnosu na sekvencijalnu bilateralnu ili samo unilateralnu kohlearnu implantaciju, kao i u odnosu na bimodalnu stimulaciju (kohlearni implant + slušno pomagalo). U svijetu se bilateralna kohlearna implantacija intenzivnije počela primjenjivati u prvom desetljeću novog milenija. U Hrvatskoj je simultana bilateralna kohlearna implantacija, kao i sekvencijalna bilateralna kohlearna implantacija, započela s primjenom 2018. godine, odlukom nacionalnog povjerenstva za kohlearnu implantaciju. Slijedeći međunarodne smjernice kohlearne implantacije, nacionalno povjerenstvo je odlučilo da gluha djeca, kao suvremeni standard otokirurškog zbrinjavanja gluhoće, dobiju dvije umjetne pužnice tvrtki Cochlear ili Med-El, koje će biti ugrađene u jednom otokirurškom postupku. Odrasli, uz ove dvije tvrtke, mogu dobiti još i Advanced Bionics umjetne pužnice, i to unilateralno. Na taj način su u Hrvatskoj zastupljene sve relevantne svjetske tvrtke umjetnih pužnica, poput drugih zemalja koje prednjače u programima kohlearne implantacije. Bilateralna kohlearna implantacija ima puno prednosti: nema „head shadow“ efekta, bolja je lokalizacija izvora i smjera zvuka, bolja je razumljivost i u tišini i u buci, a proces rehabilitacije sluha brže napreduje. Optimalni rezultati postižu se bilateralnom ugradnjom umjetnih pužnica u dobi između 12. i 24. mjeseca starosti djeteta. Nedostaci su produljeno vrijeme operativnog zahvata, dvostruki rizik oštećenja osjetljivih struktura uha, te ograničena financijska sredstva namijenjena nabavi umjetnih pužnica. Studije pokazuju da je istovremena ugradnja umjetnih pužnica kod djece bolja u odnosu na odgođenu ugradnju dviju umjetnih pužnice, kao i u odnosu na jednostranu ugradnju umjetne pužnice.

Kronična upala uha s kolesteatomom je bolest kod koje rijetko dolazi u obzir konzervativni pristup. Jedina metoda koja omogućuje izlječenje je kirurgija. Prilikom razmišljanja o sluhu nakon operacije, ne smijemo zaboraviti da je primarni cilj operacije eradikacija kolesteatoma. Između ostaloga poželjno je postići sigurno i suho uho, uho koje nije ovisno o čestoj njezi i kao bonus uho koje podnosi vodu. Preoperativni prag sluha dobro korelira s konačnim sluhom. Proširenost bolesti i prisutna destrukcija uvjetuje potrebu za radikalnošću zahvata, odnosno tipom operacije i mogućnost žrtvovanja slušnih koščica. Zatvorene tehnike daju bolje funkcionalne rezultate i bolji prag sluha. Prisutnost stapesa povezana je s boljim pragom sluha postoperativno. Velika perforacija, učestalo curenje i nedostatak manubriuma maleusa, povezani su s lošijim sluhom. Postavljanje hrskavice u područje neomembrane omogućiti će čuvanje dubine kavuma timpani i postavljanje slušne proteze. Danas je moguće dobro planiranje operacije na temelju kvalitetne radiološke obrade. Dan prije operacije bolesnika valja pregledati, te obaviti s njim razgovor, uz podsjećanje na kirurški postupak i komplikacije. Treba spomenuti mogućnost pogoršanja sluha. Rano postoperativno postoje tri razloga za takvu mogućnost. Prvi je slušanje preko bolesti kao kolumele, drugi je žrtvovanje slušnih koščica radi uklanjanja bolesti, a treći je zamjedbeni gubitak zbog oštećenja labirinta.

Summary The human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived from human, gorilla, and chimpanzee cells to study developmental mechanisms driving evolutionary brain expansion. We find that neuroepithelial differentiation is a protracted process in apes, involving a previously unrecognized transition state characterized by a change in cell shape. Furthermore, we show that human organoids are larger due to a delay in this transition, associated with differences in interkinetic nuclear migration and cell cycle length. Comparative RNA sequencing (RNA-seq) reveals differences in expression dynamics of cell morphogenesis factors, including ZEB2, a known epithelial-mesenchymal transition regulator. We show that ZEB2 promotes neuroepithelial transition, and its manipulation and downstream signaling leads to acquisition of nonhuman ape architecture in the human context and vice versa, establishing an important role for neuroepithelial cell shape in human brain expansion., Graphical abstract, Highlights • Human brain organoids are expanded relative to nonhuman apes prior to neurogenesis • Ape neural progenitors go through a newly identified transition morphotype state • Delayed morphological transition with shorter cell cycles underlie human expansion • ZEB2 is as an evolutionary regulator of this transition, Cerebral organoid models reveal that differences in the duration of a developmental transitional state driven by the factor ZEB2 underlie the basis of brain expansion in humans in comparison to great apes.

The presence of male-female brain differences has long been a controversial topic. Yet simply negating the existence of biological differences has detrimental consequences for all sexes and genders, particularly for the development of accurate diagnostic tools, effective drugs and understanding of disease. The most well-established morphological difference is size, with males having on average a larger brain than females; yet a mechanistic understanding of how this difference arises remains to be elucidated. Here, we use brain organoids to test the roles of sex chromosomes and sex steroids during development. While we show no observable differences between XX and XY brain organoids, sex steroids, namely androgens, increase proliferation of cortical neural progenitors. Transcriptomic analysis reveals effects on chromatin remodelling and HDAC activity, both of which are also implicated in the male-biased conditions autism spectrum disorder and schizophrenia. Finally, we show that higher numbers of progenitors result specifically in increased upper-layer excitatory neurons. These findings uncover a hitherto unknown role for male sex hormones in regulating excitatory neuron number within the human neocortex and represent a first step towards understanding the origin of human sex-related brain differences.

Iznenadna zamjedbena nagluhost je naglo nastali, uglavnom jednostrani, zamjedbeni gubitak sluha nepoznatog uzroka. Dijagnozu je potrebno postaviti što prije, jer raniji početak liječenja povećava vjerojatnost oporavka. Klinički pregled uključuje otoskopiju i akumetrijske testove. Dijagnoza iznenadne zamjedbene nagluhosti potvrđuje se tonskom audiometrijom, koju bi trebalo učiniti unutar nekoliko dana od nastanka smetnji. Rutinske laboratorijske krvne pretrage nisu potrebne, kao ni kompjutorizirana tomografija (CT) mozga. Inicijalno sistemsko liječenje kortikosteroidima najbolje je primijeniti unutar dva tjedna od nastanka simptoma, a prema nekim istraživanjima kortikosteroide ima smisla početi davati najkasnije šest tjedana od nastanka oštećenja. Kao inicijalno liječenje može se primijeniti i terapija kisikom u hiperbaričnoj komori (HBOT) koju je također najbolje primijeniti unutar dva tjedna od nastanka simptoma, te u iduća dva tjedna kao terapiju spašavanja. Kortikosteroidi i HBOT mogu se kombinirati. Intratimpanalna primjena kortikosteroida može se primijeniti u slučaju neuspjeha prethodne terapije, kao terapija spašavanja, do isteka ukupno šest tjedana od nastanka zamjedbenog oštećenja sluha, a iznimno kao inicijalno liječenje kod bolesnika kod kojih su sistemski kortikosteroidi i HBOT kontraindicirani. Liječenje antivirusnim, tromobolitičkim i vazodilatatornim lijekovima nije indicirano. Spontani oporavak kreće se od 31 do 70%, a uz pomoć neke od navedenih terapija taj se postotak kreće od 80 do 85%.

Purpose This article investigates the possible connections between the level of chronic stress and success of steroid therapy in patients with sudden sensorineural hearing loss (SSNHL). Method A single-center, retrospective, longitudinal cohort study on 55 patients in a tertiary referral otology center was examined. Patients diagnosed with SSNHL between 2014 and 2017 were asked to complete a Measure of Perceived Stress (Brajac, Tkalcic, Dragojević, & Gruber, 2003 ) questionnaire. Inclusion criteria were patients > 18 years of age, SSNHL diagnosed within 4 previous weeks, completed steroid treatment, and complete documentation. Results There were 30 patients (55%) that showed significant improvement in their pure-tone audiogram (PTA) hearing threshold average (≥ 15 dB) after steroid treatment. Two-step cluster analysis identified 3 clusters based on average PTA hearing threshold recovery and average Measure of Perceived Stress scores. The difference between pretreatment and posttreatment hearing levels was significantly higher in the cluster with moderate stress compared to clusters with mild and high stress levels (Kruskal–Wallis test, Friedman test, p < .001). There were no significant differences in average PTA hearing threshold recovery after steroid therapy between groups of patients with mild and severe stress. Conclusion Patients with moderate stress levels show significantly better results after steroid treatment for SSNHL than patients with low or high stress levels.

The ability to model human brain development in vitro represents an important step in our study of developmental processes and neurological disorders. Protocols that utilize human embryonic and induced pluripotent stem cells can now generate organoids which faithfully recapitulate, on a cell-biological and gene expression level, the early period of human embryonic and fetal brain development. In combination with novel gene editing tools, such as CRISPR, these methods represent an unprecedented model system in the field of mammalian neural development. In this review, we focus on the similarities of current organoid methods to in vivo brain development, discuss their limitations and potential improvements, and explore the future venues of brain organoid research., Highlights • Brain organoids currently model early human embryonic and fetal brain development to a remarkably high degree. • Brain organoids successfully model several neurodevelopmental conditions – microcephaly, idiopathic autism, Zika infection. • Modeling later neurodevelopmental events will require improvements to nutrient supply and sustained culture conditions.

Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type. © The Author 2011., This work was supported by the Strategic Research Program for Brain Sciences from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan to E.S. and H.O. and by ‘‘Funding Program for World-leading Innovative R&D on Science and Technology’’ to E.S. and H.O. W.B.H. was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (SFB 655, A2; TRR 83, Tp6) and the European Research Council (250197), by the DFG-funded Center for Regenerative Therapies Dresden, and by the Fonds der Chemischen Industrie. V.B. was supported by grants from the International Human Frontier Science Program Organization (CDA0027/2007-C), MICINN (SAF2009-07367), and CONSOLIDER (CSD2007-00023).

Basal radial glia (bRG) is a recently identified major type of neural stem cell in fetal primate, notably human, neocortex. In this issue of Neuron, Betizeau et al. (2013) now demonstrate that four morphologically distinct bRG subtypes exist in the outer subventricular zone of fetal macaque neocortex, and reveal an unexpected complexity of lineages generating neurons.

PURPOSE: The study was designed to assess correlations between intraoperative findings in revision tympanomastoidectomy as predictors of cholesteatoma recurrence. ----- MATERIALS AND METHODS: A retrospective single-institution cohort of 101 patients who underwent surgical treatment for recurrent chronic otitis media in a tertiary referral otology centre. ----- RESULTS: Out of 101 patients, 65 had canal wall up and 36 canal wall down revision surgery. There were 35 cholesteatoma recurrences. Sites most commonly associated with recurrent disease were residual facial ridge cells in 46 (45.5%), ossicular chain sites in 46 (45.5%) patients, posterior external auditory canal wall erosions in 38 (37.6%) patients and mastoid apex recurrence in 35 (34.7%) patients. Ossicular and posterior external auditory canal wall erosion and incomplete removal of mastoid apex cells correlate well with cholesteatoma recurrence accompanied by canal wall up surgery (p=0.009). Residual mastoid apex cells, posterior external auditory canal wall erosion and presence of residual facial ridge cells were identified as the strongest positive predictors of cholesteatoma recurrence, identifying high risk patients associated with canal wall down procedures (p=0.0036). ----- CONCLUSIONS: Correlations between intraoperative findings and cholesteatoma recurrence could improve preoperative and intraoperative planning and reduce the rates of postoperative failures1 due to mismanagement of high risk areas.

Recent breakthroughs in pluripotent stem cell technologies have enabled a new class of in vitro systems for functional modeling of human brain development. These advances, in combination with improvements in neural differentiation methods, allow the generation of in vitro systems that reproduce many in vivo features of the brain with remarkable similarity. Here, we describe advances in the development of these methods, focusing on neural rosette and organoid approaches, and compare their relative capabilities and limitations. We also discuss current technical hurdles for recreating the cell-type complexity and spatial architecture of the brain in culture and offer potential solutions.

A major cause of the cerebral cortex expansion that occurred during evolution is the increase in subventricular zone (SVZ) progenitors. We found that progenitors in the outer SVZ (OSVZ) of developing human neocortex retain features of radial glia, in contrast to rodent SVZ progenitors, which have limited proliferation potential. Although delaminating from apical adherens junctions, OSVZ progenitors maintained a basal process contacting the basal lamina, a canonical epithelial property. OSVZ progenitor divisions resulted in asymmetric inheritance of their basal process. Notably, OSVZ progenitors are also found in the ferret, a gyrencephalic nonprimate. Functional disruption of integrins, expressed on the basal process of ferret OSVZ progenitors, markedly decreased the OSVZ progenitor population size, but not that of other, process-lacking SVZ progenitors, in slice cultures of ferret neocortex. Our findings suggest that maintenance of this epithelial property allows integrin-mediated, repeated asymmetric divisions of OSVZ progenitors, providing a basis for neocortical expansion.

Cnidarians, the sister group to bilaterians, have a simple diffuse nervous system. This morphological simplicity and their phylogenetic position make them a crucial group in the study of the evolution of the nervous system. The development of their nervous systems is of particular interest, as by uncovering the genetic programme that underlies it, and comparing it with the bilaterian developmental programme, it is possible to make assumptions about the genes and processes involved in the development of ancestral nervous systems. Recent advances in sequencing methods, genetic interference techniques and transgenic technology have enabled us to get a first glimpse into the molecular network underlying the development of a cnidarian nervous system—in particular the nervous system of the anthozoanNematostella vectensis. It appears that much of the genetic network of the nervous system development is partly conserved between cnidarians and bilaterians, with Wnt and bone morphogenetic protein (BMP) signalling, andSoxgenes playing a crucial part in the differentiation of neurons. However, cnidarians possess some specific characteristics, and further studies are necessary to elucidate the full regulatory network. The work on cnidarian neurogenesis further accentuates the need to study non-model organisms in order to gain insights into processes that shaped present-day lineages during the course of evolution.

Expansion of the neocortex is a hallmark of human evolution. However, it remains an open question what adaptive mechanisms facilitated its expansion. Here we show, using gyrencephaly index (GI) and other physiological and life-history data for 102 mammalian species, that gyrencephaly is an ancestral mammalian trait. We provide evidence that the evolution of a highly folded neocortex, as observed in humans, requires the traversal of a threshold of 10^9 neurons, and that species above and below the threshold exhibit a bimodal distribution of physiological and life-history traits, establishing two phenotypic groups. We identify, using discrete mathematical models, proliferative divisions of progenitors in the basal compartment of the developing neocortex as evolutionarily necessary and sufficient for generating a fourteen-fold increase in daily prenatal neuron production and thus traversal of the neuronal threshold. We demonstrate that length of neurogenic period, rather than any novel progenitor-type, is sufficient to distinguish cortical neuron number between species within the same phenotypic group., Comment: Currently under review; 38 pages, 5 Figures, 13 Supplementary Figures, 2 Tables

Gyrencephaly (the folding of the surface of the neocortex) is a mammalian-specific trait present in almost all mammalian orders. Despite the widespread appearance of the trait, little is known about the mechanism of its genesis or its adaptive significance. Still, most of the hypotheses proposed concentrated on the pattern of connectivity of mature neurons as main components of gyri formation. Recent work on embryonic neurogenesis in several species of mammals revealed different progenitor and stem cells and their neurogenic potential as having important roles in the process of gyrification. Studies in the field of comparative neurogenesis revealed that gyrencephaly is an evolutionarily labile trait, and that some species underwent a secondary loss of a convoluted brain surface and thus reverted to a more ancient form, a less folded brain surface (lissencephaly). This phenotypic reversion provides an excellent system for understanding the phenomenon of secondary loss. In this review, we will outline the theory behind secondary loss and, as specific examples, present species that have undergone this transition with respect to neocortical folding. We will also discuss different possible pathways for obtaining (or losing) gyri. Finally, we will explore the potential adaptive consequence of gyrencephaly relative to lissencephaly and vice versa.

In two recent TiG articles, Gerald Crabtree argues that there is an ongoing, and inevitable, decline in the average intellect of the human species [1,2]. Crabtree attributes this purported decline to various different phenomena, although chief among them is the suggestion that the genes underpinning human intellect are uniquely susceptible to accumulating deleterious germline and somatic mutations. Germline mutations, it is argued, will gradually accumulate in intellectual deficiency (ID) genes in human populations because the genes underlying human intellect are numerous and recent estimates of the germline deleterious mutation rate suggest that de novo mutations occur in every individual.

Mota and Herculano-Houzel (Reports, 3 July 2015, p. 74) assign power functions to neuroanatomical data and present a model to account for evolutionary patterns of cortical folding in the mammalian brain. We detail how the model assumptions are in conflict with experimental and observational work and show that the model itself does not accurately fit the data.

The neocortex is the evolutionarily newest and most complex part of the mammalian brain. The neurons of the neocortex are born from different neural stem and progenitor cells (for simplicity collectively referred to as progenitors) that reside in proliferative zones during embryonic development. During the neurogenic period, distinct populations of neural progenitors appear, each having specific molecular and cell biological characteristics. These characteristics and the environment of the neural progenitor are responsible for the self-renewing or neurogenic potential of each neural progenitor type. The fate of daughter cells after neural progenitor division is determined by the mode of division, intrinsic factors such as transcription factors or regulatory ribonucleic acids (RNAs), and by extrinsic signals coming from the surrounding cells. This tight regulation controls the rate of production of neural progenitor types and neurons. The ratios of different progenitor types have a huge impact on the final number of neurons in the adult neocortex, and are partly responsible for vast differences in the brains of different mammals. Key Concepts: Neocortex is a part of the brain characteristic of mammals. Neocortex is a six-layered structure comprised of post-mitotic neurons and glial cells. Neocortical neurons are born from neural progenitor cells, mostly during embryonic development. Neural progenitor cells can be classified into different populations based on molecular and cell-biological features. The molecular and cell-biological features of neural progenitor cells influence their propensity to self-renew or produce neurons. Neural progenitor cells are under tight intrinsic and extrinsic control, in order to maintain the equilibrium between proliferative and neurogenic divisions. The relative abundance of different progenitor populations influences the final number of neurons in the adult neocortex. Keywords: mammals; neurogenesis; neocortex; neural progenitor; (a)symmetric division; evolution

The impact of tobacco cessation training of medical students on their attitude towards smoking was assessed by a validated questionnaire between final year medical students of the University of Zagreb (UZMS) and Michigan (UMMS) medical schools. UMMS students demonstrated significantly higher knowledge of tobacco cessation techniques as well as lower overall numbers of smokers in their cohort, which was attributed to targeted teaching they have received with regards to health risks of tobacco smoking.

Prilog prikazuje potragu za velikim prostim brojevima. Govori se o GIMPS projektu...