oultry bits”

Feather lice are host-specific parasites of birds that feed onthe downy regions of feathers, causing energetic stress that leadsto a reduction in host fitness through reduced survival and matingsuccess (Clayton et al. 2015). Feather lice depend on feathers forefficient locomotion. Thus, transmission between host individu-als usually requires direct contact, such as that between parentbirds and their offspring in the nest. However, feather lice canalso disperse by hitchhiking phoretically on parasitic flies thatare less host-specific than lice (Harbison and Clayton 2011). Asa consequence, lice periodically end up on novel host species(Clayton et al. 2015). Birds combat lice by removing them withtheir beaks during regular bouts of preening. Lice are thought toescape from preening through background matching crypsis be-cause light colored bird species have light colored lice, whereasdark colored species have dark colored lice (Bush et al. 2010)(Fig. 1A and B). Although these observations suggest that preen-ing is the selective agent responsible for the evolution of crypticcoloration in feather lice, this hypothesis has never been testedexperimentally

C. columbae

Host-mediated selection

phytophagou

Host species are analogous to islands that limit dispersal and geneflow between parasite populations and species. Nevertheless, asin the case of physical islands, the barriers created by host islandsare not absolute because even host-specific parasites occasionallyswitch host lineages over macroevolutionary time

crypsis

ongeneric

Adaptive radiation

To further prove that the skin organoids resemble and mimicthe physiological function of human skin tissue

quiescent

2.1. Comprehensive Proteomics Landscape of Clinical COVID-19

ymphocyte infil-tration was observed in COVID-19 skin

cells and hair follicle stem cells (HFSCs

Embryonic tissues are the mostefficiently reprogrammed, producing iPSCs that are nearly identical tofESCs. In contrast, reprogramming from accessible adult tissues, mostapplicable for modelling diseases and generating therapeutic cells, isinefficient and limited by barriers related to the differentiation stateand age of the donor’s cells4–6.

iPSCs from mouse embryo fibroblasts generate ‘all-iPSC mice’after injection into tetraploid blastocysts2 , thereby satisfying the moststringent criterion of pluripotency

re we observe thatlow-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming

in asmall number of random, widely separated dividing cells.

located diploid cells thatlack Prospero

Prospero

Allatostatin 3 and Tachykinin

SCs adjoin only the basementmembrane

tem cellshave not been described in the intestines of flies

enterocytes

Drosophila

POSTN

lungs

etastatic proces

Interactions between cancer stem cells and their

rosette-derived grafts had few TH1 neurons, did not producesignificant reductions in rotation behaviour (Fig. 4d) and showedmassive neural overgrowth

Initial studies using day 25 cells innon-lesioned adult mice showed robust survival of PSC-derivedFOXA21/TH1 neurons at 6 weeks after transplantation (Supplemen-tary Fig. 8)

neurons

metabolites DOPAC

TH1

all three conditions yielded TUJ11 neurons (Fig. 2a) andcells expressing TH, the rate-limiting enzyme in the synthesis of DA.However, only the LSB/S/F8/CHIR group yielded TH1 cells coexpres-sing LMX1A and FOXA2 as well as the nuclear receptor NURR1

3 to day 11

CHIR

neurons

Here

Wnt

FOXA2 and the roof platemarker LMX1A

FOXA2

Parkinson’s disease

eural over-growth

performance

lagged behind

Dopamine neurons derived from human ES cellsefficiently engraft in animal models ofParkinson’s disease

Nearly a

GSIS

Patients transplanted with cadaveric human is-lets can be made insulin independent for 5 years or longer via thisstrategy, but this approach is limited because of the scarcity andquality of donor islets

Byusing sequential modulation of multiple signaling pathways in athree-dimensional cell culture system, without any transgenesor genetic modification, we generate glucose-responsive,monohormonal insulin-producing cells that show key featuresof a bona fide b cell, including coexpression of key b cell markersand b cell ultrastructure.

Attempts to date at generatinginsulin-producing (INS+) cells from human pancreatic progeni-tors in vitro have generated cells with immature or abnormalphenotypes

in vivo differentiation wouldalso occur in human patients

Type 1 diabetes results from autoimmune destruction of bcells in the pancreatic islet

mice

Generation of Functional Human

hCiPS cells from human adult somatic cells

Establishing a human pluripotency network

Chemically induced dedifferentiation

we demonstrated that chemical stimulation can reprogram mousesomatic cells to PS cells by simple exposure to small molecules 8–10. Thischemical reprogramming approach synergistically targets cell signallingpathways and epigenetic modifiers without gene manipulation

These data indicate that the combination ofOct3/4, c-Myc, and Klf4 can activate the Fbx15 locus,but the change induced by these three factors alone is dif-ferent from that seen in iPS-MEF4 or iPS-MEF10 cells

G418-resistant colonies didnot form when either Oct3/4 (factor 14) or Klf4 (factor 20)was removed. Removal of Sox2 (factor 15) resulted inonly a few G418-resistant colonies. When we removedc-Myc (factor 22), G418-resistant colonies did emerge,but these had a flatter, non-ES-cell-like morphology. Re-moval of the remaining factors did not significantly affectcolony numbers. These results indicate that Oct3/4, Klf4,Sox2, and c-Myc play important roles in the generationof iPS cells from MEFs

Combination of these 10 genes alone producedmore ES cell-like colonies than transduction of all 24genes did (Figure 2B

By contrast, the Oct3/4 promoter remainedmethylated in these cells

demethylate

study

To evaluate these 24 candidate genes, we developedan assay system in which the induction of the pluripotentstate could be detected as resistance to G418

We expected thateven partial activation of the Fbx15 locus would result inresistance to normal concentrations of G418

omologous recombination

We hypothesized that the factors thatplay important roles in the maintenance of ES cell identityalso play pivotal roles in the induction of pluripotency insomatic cells

Several genes that are frequentlyupregulated in tumor

Oneway to circumvent these issues is the generation of plu-ripotent cells directly from the patients’ own cells

SUMMARY

Our data suggest that feedforward regulationis an important feature of human ES cells as well

Taken to-gether, these data support the model that OCT4, SOX2,and NANOG functionally regulate the genes they oc-cupy and suggest that loss of these regulators upondifferentiation results in increased expression of genesnecessary for development and reduced expression ofa set of genes required for the maintenance of stemcell identity

ES cells lackingthe machinery that processes miRNA transcripts are un-able to differentiate

First, thegenes occupied by OCT4 in our analysis included manypreviously identified or supposed target genes in mouseES cells or genes whose transcripts are highly enrichedin ES cells

Studies in a broad range ofeukaryotes have shown that transcriptional regulatorsthat have key roles in cellular processes frequently reg-ulate other regulators associated with that process

OCT4 is known to interact with other transcriptionfactors to activate and repress gene expression inmouse ES cells

OCT4/POU5F1 and NANOG

An understanding ofthe transcriptional regulatory circuitry that is responsi-ble for pluripotency and self-renewal in human ES cellsis fundamental to understanding human developmentand realizing the therapeutic potential of these cells.

CT4, SOX2, and NANOG

Core Transcriptional Regulatory Circuitry

result from the death or dysfunc-tion of just one or a few cell types

Teratomas

could identify gene targets for new drugs,genes that could be used for tissue regen-eration therapies, and teratogenic or toxiccompounds

ture of the human embryo.

ig. 3.

Fig. 2.

Human ES cells should offer insightsinto developmental events that cannot bestudied directly in the intact human embryobut that have important consequences inclinical areas, including birth defects, in-fertility, and pregnancy loss. Particularly inthe early postimplantation period, knowl-edge of normal human development islargely restricted to the description of a

endoderm and trophoblast differentiation(20)

he human ES cell lines maintained thepotential to form derivatives of all threeembryonic germ layers. All five cell linesproduced teratomas after injection into se-vere combined immunodeficient (SCID)–beige mice. Each injected mouse formed ateratoma, and all teratomas included gutepithelium (endoderm); cartilage, bone,smooth muscle, and striated muscle (meso-derm); and neural epithelium, embryonicganglia, and stratified squamous epithelium(ectoderm

their homogeneous appearance

tween early mouse and human development.

he high level of telomerase activityexpressed by the human ES cell lines there-fore suggests that their replicative life-spanwill exceed that of somatic cells.

Embryos were cultured to the blastocyststage, 14 inner cell masses were isolated,and five ES cell lines originating from fiveseparate embryos were derived, e

Nonhuman primate ES cell linesprovide an accurate in vitro model for un-derstanding the differentiation of humantissues (4, 5)

derivation from the pre-implantation or periimplantation embryo,(ii) prolonged undifferentiated prolifera-tion, and (iii) stable developmental poten-tial to form derivatives of all three embry-onic germ layers even after prolonged cul-ture (4)

teratocarcinoma-derivedpluripotent embryonal carcinoma (EC)cells (2)

totipotent

Human blastocyst

non-disoriented turtles.

crawls.

areas.

María Josefa, (Bernarda’s mother), aged eighty

If she looked like a broomstick with clothes on at twenty,what is she now at forty!

: No, we’re not. You serve me, and I pay you. Nothing more!

) Pepe el Romano was with the mourners.

) Bernarda!

Antonio María Benavide

bereft.

Magdalena

In

For the 13 months in which data forChthamiiailus was availabl

alanus

Comlpetition

The main purpose of this study was to de-termine the cause of death of those Chthamalusthat settled below M.H.\V.

Balanuis balanoide

Lack1954, MacArthur 1958)

Interspecific

39 % offemales were sexually active in HD zones compared to75 % of females in LD zones.

we found a negative effect of densityon recruitment and reproduction. In contrast, density had aslightly positive effect on survival indicating that mortalitydid not drive the steeper declines in animal numbers at highdensit

Zamboanga City began as a military outpost built to contain Moslem penetration in the southern Philippines. Fort Pilar, the main defense, was constructed in the 1630s but was abandoned some 30 years later due to repeated attacks. Spaniards returned to Zamboanga in 1719, and the subsequent Spanish presence in that area was con- tinuous until 1898

Manila Bay dialects,

reole language

ncluding Z (the main focus of his article): “Philippine Creole Spanish is not simply a Philippine language with unusually heavy Spanish lexical influence, nor is it Spanish with a large number of Philippine loan words. It is a distinct language, easily distinguishable from both its Romance and its Austronesian progenitors. Philippine Creole Spanish shares enough in common with the classic creoles of the Caribbean

Tematefio (T)

More recently, the predominant source of lexical borrowing has become Eng- lish, as in all other Philippine languages; not only are individual words bor- rowed, but entire expressions may be introduced into Chabacano speech, and among those speakers reasonably fluent in English, code switching is common.9 Nouns and some verbs may simply be given a Chabacano form, much as occurs in bilingual Spanish/English speech in the United States: sacrificid 'sacrifice' (Sp. sacrificar), compositd 'compose' (Sp. componer), dependable 'depend- able' (Sp. conflable), dolyar 'dollar' (Sp. dolar), valuable 'valuable' (Sp. val- ioso), serioso 'serious' (Sp. serio), preliminario 'preliminary' (Sp. preliminar), and so forth. These loan translations may arise spontaneously, in a conversation or a radio program, or may be widely used by large segments of the population. Chabacano also makes extensive use of the Visayan prefix man-; originally this prefix formed verbs from Spanish and Visayan nouns (man-cuento 'to chat', man-encuentro 'to meet', man-ulan 'to rain', man-gulu 'to make trouble'), but currently, any English word or expression (not necessarily a noun) may be converted into a Chabacano verb by means of this ppefix: man-relax, man- takeover, man-kidnap, man-turnover, man-public service ('make a public ser- vice announcement'). This is an active process and any English word may be used, even when equivalent Chabacano words are

Traditionally, Zamboanguefios have considered Chabacano to be "broken Spanish" (the term most frequently used by Zamboanguenos themselves and by many Spanish-speaking foreigners) and have asserted that PCS "has no gram- mar," a sentiment commonly voiced in other creole-speaking areas (e.g., Craig (1977:315]; Tinelli [I983:69]). A concomitant to this feeling is the belief that any Chabacano speaker can completely understand Spanish and that perhaps only laziness and lack of practice prevents Zamboanguenios from speaking "real" Spanish; at the same time, it is supposed that any native Spanish speaker can immediately and flawlessly understand and use Chabacano, simply by "degrad- ing" his or her own Spanish

Studies on Zamboanguefio carried out in the early I950S (e.g., McKaughan 1954; Whinnom 1956) gave the impression that this language was on the verge of extinction, but in all probability the population of PCS speakers is actually growing in Zamboanga (Frake I971)

the incorporation of recent/contemporary Spanish elements which commenced several generations ago and which to a certain extent continues to take place, despite the fact that virtually no one in Zamboanga is truly proficient in Spa

decreolization

Chabacano/Spanish and the Philippine linguistic identity

aristocratic authenticity

assert that Philippine Creole Spanish is but a relexification of a pan-Asian Portuguese-based creole. All other Spanish-based creoles (Papiamentu, Afro-Colombian Palenquero, and vestigial enclaves found in Latin America) result from Afro-Hispanic language contacts, although some Hispano

The failure of the Spanish language to establish itself in the Philippines

Spanish was pushed ever further into the background

English

three distinct dialects still exist, in Ternate, Cavite and Zamboanga.

6

5

4

3

2

Philippine Creole Spanish dialects were once spoken more extensively in the Ermita district of Manila as well as in other enclaves on Manila Bay (Cavite and Ternate), but most non-speakers of Manila Bay Chabacano who were even aware that some Spanish-derived language was spoken in their midst assumed that this was some form of Spanish, possibly a broken second-language variety or pidgin.

Zamboanga City and surrounding parts of Zamboanga del Sur province, as well as in other pockets in Mindanao and the islands of Basilan and Jolo.

ignored by many, repudiated by those who aware of its existence

Although within the PCS/Chabacano-speaking communities this word has lost the negative connotation and refers only to the language itself, many enlightened community members avoid the term Chabacano and prefer instead the regional designations of Caviteño, Ternateño, and especially Zamboangueño.

Philippine Creole Spanish, and to the speech communties themselves as Chabacano.

The amount of Spanish lexical incursions into the major Philippine language families is beyond dispute; less well understood is the extent to which the Spanish language is actively used and understood throughout the nation